- An 3-Indolyl-imidazol-4-one from the Tunicate Dendrodoa grossularia.
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A new compound, possessing an unususal 4H-imidazole ring was isolated; structure elucidation was performed using spectral analysis and confirmed by synthesis.
- Guyot, Michele,Meyer, Michele
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- A general synthesis of tris-indole derivatives as potential iron chelators
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The development of a novel route for the synthesis of a new class of compounds is described. The first tripodal, tris-indole amines are prepared by straightforward routes.
- Sears, R. Bryan,Carpenter, Russell A.,Whitlock, Christine R.
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- Rationally designed tri-armed imidazole–indole hybrids as naked eye receptors for fluoride ion sensing
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The present communication describes the design, synthesis, and characterization of unique tri-armed imidazole–indole hybrids RA-RE for naked eye detection of fluoride ion in 9:1 DMSO–water at concentration level of 1.5 ppm, which is recommended permissible limit of fluoride ion. Molecular structures of the receptors are so fabricated that both heterocyclic units, namely, indole and imidazole have been rationally used as chromophore and binding unit, respectively. Strategical introduction of nitro group(s) at the fifth position of indole ring remarkably enhances the binding ability of receptor RD making it highly selective toward fluoride ion (tetrabutylammonium salt) over other typical anionic species. The sensing event can be visualized by naked eyes swiftly with color change. This observation is well corroborated by a redshift of 80 nm in UV–visible spectroscopic studies. A peak at 16.1 ppm due to HF2- in 1H NMR titration validates the deprotonation of imidazolium N?H by fluoride ion.
- Jain, Anshu,Gupta, Ragini,Agarwal, Madhu
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- N-1, C-3 substituted indoles as 5-LOX inhibitors - In vitro enzyme immunoaasay, mass spectral and molecular docking investigations
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Based upon the structures of some known 5-LOX inhibitors, a set of five compounds carrying appropriate substituents at N-1 and C-3 of indole were synthesized and investigated for 5-LOX inhibitory activities. Fifty percent inhibitory concn (IC50) of these compounds ranges from 0.6 to 5 μM and found to be comparable to that of clinically used 5-LOX inhibitor, zileuton. The compounds under present investigations exhibited appreciable interactions with 5-LOX as apparent from their association constants calculated from the mass spectral data. Compound 5a with a tosyl group at N-1 and pyrolidinyl-1,2-dione substituent at C-3 of indole, exhibiting IC50 0.6 μM and stoichiometry of 1:7 in the enzyme-compound complex was identified as highly potent 5-LOX inhibitor and seems to be suitable for further investigations.
- Singh, Palwinder,Pooja
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- Rational modification of a lead molecule: Improving the antifungal activity of indole – triazole – amino acid conjugates
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The modification of a molecule that was identified as highly efficacious in the previous studies could considerably improve the biological activity of the resulting compounds. While targeting lanosterol 14-α demethylase, the molecular modelling studies convinced that the extension of the phenyl ring of compound 1 deep into the hydrophobic pocket of the enzyme may increase the enzyme – ligand interactions and hence improve the anti-fungal profile of the molecules. As a result, the newly designed compounds 2 were synthesized and screened for their anti-microbial properties and these compounds were found to exhibit considerably better activity than the previous molecule 1. Some of the compounds in this series exhibited MIC90 16 μg mL?1 and 32 μg mL?1 against Candida albicans and Aspergillus niger, respectively as against 312 μg mL?1 for compound 1.
- Mishra, Sahil,Kaur, Manpreet,Chander, Subhash,Murugesan, Sankaranarayanan,Nim, Lovedeep,Arora,Singh, Palwinder
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- Total synthesis and bioactivity of the marine alkaloid pityriacitrin and some of its derivatives
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We report herein the chemical synthesis and biological evaluation of β-carboline alkaloid pityriacitrin and some of its new derivatives. Using tryptophan or 5-hydroxytryptophan and 5-substituted indole-3-glyoxals as the starting materials, pityriacitrin and some of its derivatives were synthesized via the acid-catalyzed Pictet-Spengler reaction and fully characterized by 1H and 13C NMR, mass spectroscopy and IR determinations. Biological studies revealed that pityriacitrin has a weak antiproliferative activity against a panel of breast and prostate cancer cell lines, whereas some of its derivatives exhibited stronger and potent activity, which was associated with induction of both cell apoptosis and necrosis.
- Zhang, Puyong,Sun, Xiaofei,Xu, Bin,Bijian, Krikor,Wan, Shengbiao,Li, Guigen,Alaoui-Jamali, Moulay,Jiang, Tao
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- N-(indol-3-ylglyoxylyl)piperidines: High affinity agonists of human GABA-A receptors containing the α1 subunit
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A new class of N-(indol-3-ylglyoxylyl)piperidines are high affinity agonists at the benzodiazepine binding site of human GABA-A receptor ion-channels, with modest selectivity for receptors containing the α1 subunit over α2 and α3. All three receptor subtypes discriminate substantially between the two enantiomers of the chiral ligand 10. (C) 2000 Elsevier Science Ltd. All rights reserved.
- Collins, Ian,Davey, William B.,Rowley, Michael,Quirk, Kathleen,Bromidge, Frances A.,McKernan, Ruth M.,Thompson, Sally-Anne,Wafford, Keith A.
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- Receptor binding profiles and quantitative structure-affinity relationships of some 5-substituted-N,N-diallyltryptamines
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N,N-Diallyltryptamine (DALT) and 5-methoxy-N,N-diallyltryptamine (5-MeO-DALT) are two tryptamines synthesized and tested by Alexander Shulgin. In self-experiments, 5-MeO-DALT was reported to be psychoactive in the 12-20 mg range, while the unsubstituted compound DALT had few discernible effects in the 42-80 mg range. Recently, 5-MeO-DALT has been used in nonmedical settings for its psychoactive effects, but these effects have been poorly characterized and little is known of its pharmacological properties. We extended the work of Shulgin by synthesizing additional 5-substituted-DALTs. We then compared them to DALT and 5-MeO-DALT for their binding affinities at 45 cloned receptors and transporter proteins. Based on in vitro binding affinity, we identified 27 potential receptor targets for the 5-substituted-DALT compounds. Five of the DALT compounds had affinity in the 10-80 nM range for serotonin 5-HT1Aand 5-HT2Breceptors, while the affinity of DALT itself at 5-HT1Areceptors was slightly lower at 100 nM. Among the 5-HT2subtypes, the weakest affinity was at 5-HT2Areceptors, spanning 250-730 nM. Five of the DALT compounds had affinity in the 50-400 nM range for serotonin 5-HT1D, 5-HT6, and 5-HT7receptors; again, it was the unsubstituted DALT that had the weakest affinity at all three subtypes. The test drugs had even weaker affinity for 5-HT1B, 5-HT1E, and 5-HT5Asubtypes and little or no affinity for the 5-HT3subtype. These compounds also had generally nanomolar affinities for adrenergic α2A, α2B, and α2Creceptors, sigma receptors σ1and σ2, histamine H1receptors, and norepinephrine and serotonin uptake transporters. They also bound to other targets in the nanomolar-to-low micromolar range. Based on these binding results, it is likely that multiple serotonin receptors, as well as several nonserotonergic sites are important for the psychoactive effects of DALT drugs. To learn whether any quantitative structure-affinity relationships existed, we evaluated correlations among physicochemical properties of the congeneric 5-substituted-DALT compounds. The descriptors included electronic (σp), hydrophobic (π), and steric (CMR) parameters. The binding affinity at 5-HT1A, 5-HT1D, 5-HT7, and κ opioid receptors was positively correlated with the steric volume parameter CMR. At α2A, α2B, and α2Creceptors, and at the histamine H1receptor, binding affinity was correlated with the Hammett substituent parameter σp; higher affinity was associated with larger σpvalues. At the σ2receptor, higher affinity was correlated with increasing π. These correlations should aid in the development of more potent and selective drugs within this family of compounds.
- Cozzi, Nicholas V.,Daley, Paul F.
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- Synthesis of deuterium labeled tryptamine derivatives
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The synthesis of deuterium labeled tryptamine derivatives, [2-(1H-indol-3-yl)-[2H4]-ethyl]-dimethylamine (DMT), [2H10]-diethyl-[2-(1H-indol-3-yl)-ethyl]-amine (DET), [2-(1H-indol-3-yl)-ethyl]-[2H6]-dipropyl-amine (DPT) and [2H2]-alpha-methyltryptamine (AMT) is described. The isotopically labeled compounds are used as internal standards in gas chromatography-mass spectrometry (GC-MS) assays.
- Wang, Yu-Yun,Chen, Chinpiao
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- Identification of an indole-triazole-amino acid conjugate as a highly effective antifungal agent
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Compounds constructed by the grafting of amino acid and triazole with an indole moiety were synthesized and investigated for antifungal activities wherein one of the compounds gave highly promising results. Although the compound has a high MIC80 value in liquid medium, it shows significant antifungal activity against Candida albicans in solid plate assays. The compound is found to target chitin in the cell wall and lanosterol 14α-demethylase of the ergosterol biosynthesis pathway. The inhibitory effect of the compound becomes more pronounced in combination with azoles and CFW. The compound is also found to significantly affect chitin levels, cell morphology and cell viability in combination with ketoconazole.
- Pawar, Kalpana,Yadav, Anshuman,Prasher, Parteek,Mishra, Sahil,Singh, Balwinder,Singh, Palwinder,Komath, Sneha Sudha
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- An efficacious synthesis of N-1–, C-3–substituted indole derivatives and their antimicrobial studies
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A novel series of 11 C-3– and N-1–substituted oxoacetamide indole derivatives were synthesized by reacting with various aromatic amines and alkyl halides. These compounds were characterized by using various spectral techniques, ie, 1HNMR, 1HNMR-D2O, 13CNMR, UV, elemental analysis, IR, and mass spectrometery. In vitro, antimicrobial studies of resultant compounds were carried out against two bacterial strains, Pseudomonas aeruginosa and Pseudomonas oryzihabitans using disc plate method. All the tested compounds showed vital efficiency as antimicrobial agents against both the bacterial strains. The results revealed that synthesized indole derivative 2-(1-(3-bromopropyl)-1H-indol-3-yl)-N-(2-nitrophenyl)-2-oxoacetamide displayed the best antimicrobial activity as compared with all other synthesized compounds.
- Jain, Palak,Utreja, Divya,Sharma, Poonam
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- Microwave-accelerated synthesis of psychoactive deuterated N,N-dialkylated-[α,α,β,β-d4]-tryptamines
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A large number of N,N-dialkylated tryptamines are known to induce psychoactive effects in humans. This has resulted in their increased attention within clinical and forensic communities. Deuterated tryptamines are ideal for use as internal standards during MS bioanalysis or of use in biochemical NMR studies. The present study reports on a microwave-enhanced synthesis of 22 N,N-dialkylated-[α,α,β,β-d4]-tryptamines via the reduction with lithium aluminium deuteride of glyoxalylamide precursors obtained by the procedure of Speeter and Anthony. Syntheses were carried out using a single-mode system under elevated pressure conditions where anhydrous tetrahydrofuran was used as the solvent at 150°C. Good yields were obtained within 5 min. Copyright
- Brandt, Simon D.,Tirunarayanapuram, Sri Subha,Freeman, Sally,Dempster, Nicola,Barker, Steven A.,Daley, Paul F.,Cozzi, Nicholas V.,Martins, Claudia P. B.
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- The design and synthesis of novel 3-[2-indol-1-yl-ethyl]-1H-indole derivatives as selective inhibitors of CDK4
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We present the design, synthesis and biological activity of novel 3-[2-indol-1-yl-ethyl]-1H-indole selective inhibitors of CDK4.
- Aubry, Carine,Patel, Asma,Mahale, Sachin,Chaudhuri, Bhabatosh,Maréchal, Jean-Didier,Sutcliffe, Michael J.,Jenkins, Paul R.
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- Design and synthesis of newer 1,3,4-oxadiazole and 1,2,4-triazole based Topsentin analogues as anti-proliferative agent targeting tubulin
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A set of two series of 1,3,4-oxadiazole (11a-n) and 1,2,4-Triazole (12a, c, e, g, h, j-n) based topsentin analogues were prepared by replacing imizadole moiety of topsentin through a multistep synthesis starting from indole. All the compounds synthesized were submitted for single dose (10 μM) screening against a NCI panel of 60-human cancer cell lines. Among all cancer cell lines, colon (HCC-2998) and Breast (MCF-7, T-47D) cancer cell lines were found to be more susceptible for this class of compounds. Among the compounds tested, compounds 11a, 11d, 11f, 12e and 12h, were exhibited good anti-proliferative activity against various cancer cell lines. Compounds 11d, 12e and 12h demonstrated better activity with IC50 2.42 μM, 3.06 μM, and 3.30 μM respectively against MCF-7 human cancer cell line than that of the standard drug doxorubicin IC50 6.31 μM. Furthermore, 11d induced cell cycle arrest at G0/G1 phase and also disrupted mitochondrial membrane potential with reducing cell migration potential of MCF-7 cells in dose dependent manner. In vitro microtubule polymerization assays found that compound 11d disrupt tubulin dynamics by inhibiting tubulin polymerization with IC50 3.89 μM compared with standard nocodazole (IC50 2.49 μM). In silico docking studies represented that 11d was binding at colchicine binding site of β-tubulin. Compound 11d emerged as lead molecule from the library of compounds tested and this may serve as a template for further drug discovery.
- Naaz, Fatima,Ahmad, Faiz,Lone, Bilal Ahmad,Pokharel, Yuba Raj,Fuloria, Neeraj Kumar,Fuloria, Shivkanya,Ravichandran, Manickam,Pattabhiraman, Lalitha,Shafi, Syed,Shahar Yar
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- BMS Derivatives C7-Linked to β-Cyclodextrin and Hyperbranched Polyglycerol Retain Activity against R5-HIV-1NLAD8 Isolates and Can Be Deemed Potential Microbicides
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Amides from indole-3-glyoxylic acid and 4-benzoyl-2-methylpiperazine, which are related to entry inhibitors developed by Bristol-Myers Squibb (BMS), have been synthesized with aliphatic chains located at the C7 position of the indole ring. These spacers contain an azido group suitable for the well-known Cu(I)-catalyzed (3+2)-cycloaddition or an activated triple bond for the nucleophilic addition of thiols under physiological conditions. Reaction with polyols (β-cyclodextrin and hyperbranched polyglycerol) decorated with complementary click partners has afforded polyol-BMS-like conjugates that are not cytotoxic (TZM.bl cells) and retain the activity against R5-HIV-1NLAD8 isolates. Thus, potential vaginal microbicides based on entry inhibitors, which can be called of 4th generation, are reported here for the first time.
- Petit, Elena,Bosch, Lluís,Costa, Anna M.,Rodríguez-Izquierdo, Ignacio,Sepúlveda-Crespo, Daniel,Mu?oz-Fernández, M. Angeles,Vilarrasa, Jaume
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p. 2217 - 2222
(2021/05/06)
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- Novel positive allosteric modulators of A2B adenosine receptor acting as bone mineralisation promoters
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Small-molecules acting as positive allosteric modulators (PAMs) of the A2B adenosine receptor (A2B AR) could potentially represent a novel therapeutic strategy for pathological conditions characterised by altered bone homeostasis, including osteoporosis. We investigated a library of compounds (4-13) exhibiting different degrees of chemical similarity with three indole derivatives (1-3), which have been recently identified by us as PAMs of the A2B AR able to promote mesenchymal stem cell differentiation and bone formation. Evaluation of mineralisation activity of 4-13 in the presence and in the absence of the agonist BAY60-6583 allowed the identification of lead compounds with therapeutic potential as anti-osteoporosis agents. Further biological characterisation of one of the most performing compounds, the benzofurane derivative 9, confirmed that such a molecule behaves as PAM of the A2B AR.
- Barresi, Elisabetta,Giacomelli, Chiara,Marchetti, Laura,Baglini, Emma,Salerno, Silvia,Greco, Giovanni,Da Settimo, Federico,Martini, Claudia,Trincavelli, Maria Letizia,Taliani, Sabrina
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p. 286 - 294
(2020/12/22)
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- Fe-Catalyzed Pictet-Spengler-Type Cyclization via Selective Four-Electron Reductive Functionalization of CO2
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Herein, we describe a novel catalytic Pictet-Spengler-type cyclization using CO2 as a nontoxic and sustainable C1 feedstock with environmentally benign and non-precious-metal iron as catalyst. The reaction is achieved by selective four-electron reduction of CO2 into methylene level intermediate through carefully tuning the reaction parameters. A variety of tetrahydro-β-carbolines and other nitrogen-containing heterocycles can be easily obtained under mild conditions. Mechanistic studies have shown that tetrahydro-β-carbolines are probably obtained via spiroindolenine intermediates.
- Li, Wen-Duo,Chen, Jie,Zhu, Dao-Yong,Xia, Ji-Bao
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supporting information
p. 614 - 620
(2021/02/12)
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- Compound containing 2,4 - thiazole ring and preparation method and application thereof
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The invention provides a compound containing 2,4 - thiazole rings and a preparation method and application thereof, wherein the compound is shown in a formula X. A Is pyrazolopyrimidine or indole. Z Is carbonless. X Is O or S. Y Is - O - or - NH . R1 Hydrogen or C1 -6 Alkyl. R2 Be selected from C1 - C3 Alkyl. C5 - C15 Alkenyl, alkynyl, 5 - RMB 10 heterocyclic radicals, C6 - C12 Aryl, 5 -12 membered heteroaryl, sterol and 5-10 元 cycloalkyl. Y And R2 Connection, or Y and R2 Looping. R3 From hydrogen. Halogen, amino, hydroxyl, acetyl, 3 - RMB 10 heterocyclic group, C6 - C12 Aryl, 5 -12-membered heteroaryl, 3 -10-membered cycloalkyl, ester, carboxy, trihalomethyl and adamantyl. R2 Or R3 It is unsubstituted or is selected from C. 1 - C6 Alkyl. A hydroxy group, a halogen group, a trihalomethyl group, a carboxyl group, and a phenyl group. R2 Document C1 - C3 Alkyl, R3 Hydrogen.
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Paragraph 0189-0191
(2021/08/25)
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- Synthesis and anti-tumor activity of marine alkaloids
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Marine alkaloids were divided into five categories from the perspective of anti-tumor activity. The optimization process, chemical synthesis, anti-tumor activity evaluation and structure–activity relationship of various compounds were discussed.
- Chen, Guangying,Huang, Gangliang,Zhou, Shiyang
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- Indole-based heterocyclic compound as well as preparation method and application thereof in prevention and treatment of plant diseases
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The invention discloses an indole-based heterocyclic compound as well as a preparation method and application thereof in prevention and treatment of plant diseases. According to the method, indole isreacted with oxalyl chloride to obtain indole oxalyl chloride, then indole oxalyl chloride is reduced by tributylstannane to obtain indole carbonyl acetaldehyde, and finally indole carbonyl acetaldehyde is reacted with a corresponding amino acid under the catalysis of iodine to obtain a compound; or indole hydrazide is reacted with an aldehyde, and oxidizing with iodobenzene acetate is carried outto obtain the compound. The indole heterocyclic compound provided by the invention shows especially excellent plant virus resisting activity, can well inhibit the tobacco mosaic virus, and also showsbroad-spectrum plant pathogenic bacteria resisting activity.
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Paragraph 0049-0051; 0058-0059
(2020/07/15)
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- Design, synthesis, and evaluation of novel anti-trypanosomal compounds
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Human African trypanosomiasis (HAT) is a deadly neglected tropical disease caused by the protozoan parasite Trypanosoma brucei. During the course of screening a collection of diverse nitrogenous heterocycles, we discovered two novel compounds that contain the tetracyclic core of the Yohimbine and Corynanthe alkaloids, were potent inhibitors of T. brucei proliferation and T. brucei methionyl-tRNA synthetase (TbMetRS) activity. Inspired by these key findings, we prepared several novel series of hydroxyalkyl δ-lactam, δ-lactam, and piperidine analogs and tested their anti-trypanosomal activity. A number of inhibitors were more potent against T. brucei than these initial hits with one hydroxyalkyl δ-lactam derivative being 25-fold more effective in our assay. Surprisingly, most of these active compounds failed to inhibit TbMetRS. This work underscores the importance of verifying, irrespective of close structural similarities, that new compounds designed from a lead with a known biological target engage the putative binding site.
- Lepovitz, Lance T.,Martin, Stephen F.,Meis, Alan R.,Mensa-Wilmot, Kojo,Pham, Alexandra,Thomas, Sarah M.,Wiedeman, Justin
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- Design, synthesis, biological evaluation and molecular modelling studies of conophylline inspired novel indolyl oxoacetamides as potent pancreatic lipase inhibitors
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A novel series of 21 indolyl oxoacetamide analogues was designed based on the natural product lead conophylline, and evaluated for their pancreatic lipase inhibitory activity using porcine pancreatic lipase (Type II). Analogues 12c and 12b exhibited comparatively greater potential (IC50 values of 2.95 and 3.26 μM) than conophylline (IC50-3.31 μM), while the standard drug, orlistat, exhibited a potent IC50 value of 0.99 μM. Further, analogues 12b and 12c exhibited reversible competitive inhibition similar to orlistat and conophylline, and possessed Ki values of 1.89 and 1.69 μM, respectively. Molecular docking of these analogues was in agreement with the in vitro results, wherein the MolDock scores exhibited significant correlation with their inhibitory activity. A 10 ns molecular dynamics simulation of 12c complexed with pancreatic lipase confirmed the role of extended alkyl interactions, along with π-π stacking and π-cation interactions, in stabilising the ligand in the active site (maximum observed RMSD ≈ 3.5 ?). ADMET prediction indicated the GI absorption of these analogues to be high; however, they did not possess carcinogenicity and hepatotoxicity in contrast to orlistat and conophylline.
- Palawat, Saksham,Paul, Atish T.,Sridhar, S. N. C.
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p. 12355 - 12369
(2020/08/03)
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- Indole heterocyclic compound, preparation method thereof and application of indole heterocyclic compound in prevention and treatment of plant diseases
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The invention discloses an indole heterocyclic compound as well as a preparation method and application thereof in prevention and treatment of plant diseases. According to the method, indole is reacted with oxalyl chloride to obtain indole oxalyl chloride, then indole oxalyl chloride is reduced by tributylstannane to obtain indole carbonyl acetaldehyde, and finally indole carbonyl acetaldehyde isreacted with a corresponding amino acid under the catalysis of iodine to obtain a compound. The indole heterocyclic compound provided by the invention shows especially excellent plant virus resistingactivity, can well inhibit the tobacco mosaic virus, and also shows broad-spectrum plant pathogenic bacteria resisting activity.
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Paragraph 0046-0048
(2020/07/15)
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- Discovery of Pimprinine Alkaloids as Novel Agents against a Plant Virus
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Plant viral diseases cause tremendous decreases in crop yield and quality. Natural products have always been a valuable source for lead discovery in medicinal and agricultural chemistry. A series of pimprinine alkaloids and their derivatives were prepared and identified by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HR-MS). The antiviral activities of these alkaloids against tobacco mosaic virus (TMV) were systematically investigated for the first time. Most of the compounds exhibited higher antiviral activities than ribavirin. Compounds 5l, 9h, and 10h, which had similar or higher antiviral activities than ningnanmycin (perhaps the most widely used antiviral agent at present), emerged as new antiviral pilot compounds. This systematic structure-activity-relationship research lays the foundation for simplifying the structure of these alkaloids. The ring-open products, acylhydrazones 9a-9u, were also found to possess good antiviral activities. Moreover, all the synthesized compounds displayed broad-spectrum fungicidal activities. This study provides important information for the research and development of pimprinine alkaloids as novel antiviral agents.
- Liu, Bin,Li, Rui,Li, Yanan,Li, Songyi,Yu, Jin,Zhao, Binfen,Liao, Ancai,Wang, Ying,Wang, Ziwen,Lu, Aidang,Liu, Yuxiu,Wang, Qingmin
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p. 1795 - 1806
(2019/02/27)
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- Indole amide synthesis of derivatives and their use as plant growth regulators
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The invention discloses indole amide derivatives and its synthetic method, is to indole, oxalyl, aromatic amine as the main raw material, by conventional solvent method and ultrasonic radiation method for synthesis of a indolyl for the skeleton to amide derivatives. Because the indole amide in the molecule containing both indole group, but also has the amide structure, under the condition of the best concentration demonstrates the role in promoting the growth of wheat, indole acetic acid than more dominating, and therefore as a plant growth regulator is applied to the agricultural production has very good prospects.
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Paragraph 0016; 0018
(2019/07/11)
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- Design, synthesis, biological evaluation and molecular modelling studies of indole glyoxylamides as a new class of potential pancreatic lipase inhibitors
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A series of eighteen indole glyoxylamide analogues were synthesized, characterized and evaluated for their pancreatic lipase inhibitory activity. Porcine pancreatic lipase (Type II) was used with 4-nitrophenyl butyrate (as substrate) for the in vitro assay. Compound 8f exhibited competitive inhibition against pancreatic lipase with IC50 value of 4.92 μM, comparable to that of the standard drug, orlistat (IC50 = 0.99 μM). Compounds 7a-i and 8a-i were subjected to molecular docking into the active site of human PL (PDB ID: 1LPB) wherein compound 8f possessed a potential MolDock score of ?153.037 kcal/mol. Molecular dynamics simulation of 8f complexed with pancreatic lipase, confirmed the role of aromatic substitution in stabilizing the ligand through hydrophobic interactions (maximum observed RMSD = 3.5 ?).
- Sridhar,Palawat, Saksham,Paul, Atish T.
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p. 373 - 381
(2019/01/16)
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- Optimization, Structure-Activity Relationship, and Mode of Action of Nortopsentin Analogues Containing Thiazole and Oxazole Moieties
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Plant diseases seriously endanger plant health, and it is very difficult to control them. A series of nortopsentin analogues were designed, synthesized, and evaluated for their antiviral activities and fungicidal activities. Most of these compounds displayed higher antiviral activities than ribavirin. Compounds 1d, 1e, and 12a, with excellent antiviral activities, emerged as novel antiviral lead compounds, among which 1e was selected for further antiviral mechanism research. The mechanism research results indicated that these compounds may play an antiviral role by aggregating viral particles to prevent their movement in plants. Further fungicidal activity tests revealed that nortopsentin analogues displayed broad-spectrum fungicidal activities. Compounds 2p and 2f displayed higher antifungal activities against Alternaria solani than the commercial fungicides carbendazim and chlorothalonil. Current research has laid a foundation for the application of nortopsentin analogues in plant protection.
- Guo, Jincheng,Hao, Yanan,Ji, Xiaofei,Wang, Ziwen,Liu, Yuxiu,Ma, Dejun,Li, Yongqiang,Pang, Huailin,Ni, Jueping,Wang, Qingmin
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p. 10018 - 10031
(2019/10/05)
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- PHOTOPROTECTIVE COMPOSITIONS CONTAINING MALASSEZIA-DERIVED COMPOUNDS AND/OR CHEMICAL ANALOGS THEREOF
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The present invention relates to compounds, compositions, and methods for modulating skin pigmentation and treating or preventing UV-induced skin damage, erythema, aging of the skin, sunburn, and hyperpigmentation in a subject. The compounds, compositions, and methods of the present invention generally involve Malassezia-derived compounds, including malassezin and indirubin, and/or chemical analogs thereof. Other applications of the compounds and compositions disclosed herein include, but are not limited to, improving hyperpigmentation caused by a hyperpigmentation disorder, inducing melanocyte apoptosis, and modulating arylhydrocarbon receptor (AhR) activity, melanogenesis, melanin production, melanosome biogenesis, melanosome transfer, melanocyte activity, and melanin concentration.
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Paragraph 0937
(2019/11/04)
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- 1,2,3-triazole tethered Indole-3-glyoxamide derivatives as multiple inhibitors of 5-LOX, COX-2 & tubulin: Their anti-proliferative & anti-inflammatory activity
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To evaluate the role of COX-2 and 5-LOX as dual inhibitors in controlling the cancer cell proliferation, a set of two series having 42 compounds of 1, 2, 3-Tethered Indole-3-glyoxamide derivatives were synthesized by employing click chemistry approach and were also evaluated for their in vitro cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) inhibitory activities with in vivo anti-inflammatory and in vitro anti-proliferative potencies. Among the compounds tested, compounds 11q and 13s displayed excellent inhibition of COX-2 (IC50 0.12 μM) with good COX-2 selectivity index (COX-2/COX-1) of 0.058 and 0.046 respectively. Compounds 11q and 13s also demonstrated comparable 5-LOX inhibitory activity with IC50 7.73 and 7.43 μM respectively to that of standard Norhihydroguaiaretic acid (NDGA: IC50 7.31 μM). Among all the selected cell lines, prostate cancer cell line DU145 was found to be susceptible to this class of compounds. Among all the tested compounds, compounds 11g, 11i, 11k, 11q, 13r, 13s and 13u demonstrated excellent to moderate anti-proliferative activity with IC50s ranging between 6.29 and 18.53 μM. Compounds 11q and 11g demonstrated better anti-proliferative activities against DU145 cancer cell line with IC50 values 8.17 and 8.69 μM respectively when compared to the standard drug etoposide (VP16; IC50 9.80 μM). Compounds 11g, 11k, 11q, 13s and 13u showed good dual COX-2/5-LOX inhibitory potentials with excellent anti-proliferative activity. Results from carrageenan-induced hind paw edema demonstrated that compounds 11b, 11l, 11q and 13q exhibited significant anti-inflammatory activity with 69–77% inhibition at 3 h, 75–82% inhibition at 5 h when compared to the standard drug indomethacin (66.6% at 3 h and 77.94% at 5 h). Ulcerogenic study revealed that compounds 11q and 13q did not cause any gastric ulceration. In vitro tubulin assay resuted that compound 11q interfered with microtubulin dynamic and act as tubulin polymerization inhibitor. In silico molecular docking studies demonstrated that compounds 11q and 13s are occupying the colchicines binding site of tubulin polymer and 11q illustrated very good binding affinities towards COX-2 and 5-LOX.
- Naaz, Fatima,Preeti Pallavi,Shafi, Syed,Mulakayala, Naveen,Shahar Yar,Sampath Kumar
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- Use of novel haptens in the production of antibodies for the detection of tryptamines
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Tryptamines are a group of hallucinogenic drugs whose detection in body fluids could be simplified by immunochemical assay kits. Antibodies for these assays are obtained by the immunization of laboratory animals with conjugates of a hapten similar to the target analyte and a suitable protein. Therefore we synthesized novel haptens derived from tryptamine-based drugs, with N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and N,N-diisopropyltryptamine (DiPT) selected as the target analytes. Their structures were modified with a short linker ended with a carboxylic group. The haptens were conjugated with bovine serum albumin (BSA) and rabbits were immunized with the conjugates. The obtained polyclonal antibodies showed good reactivity and the LOD of the constructed ELISAs was in the range 0.006-0.254 ng mL-1. Thus, they are suitable for the development of immunochemical assay kits.
- Mary?ka, Michal,Fojtíková, Lucie,Jurok, Radek,Holubová, Barbora,Lap?ík, Old?ich,Kucha?, Martin
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p. 16243 - 16250
(2018/05/22)
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- INDOLE AHR INHIBITORS AND USES THEREOF
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The present invention provides compounds useful as inhibitors of AHR, compositions thereof, and methods of using the same.
- -
-
Paragraph 00826-00827
(2018/11/22)
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- 3-(7-Azaindolyl)-4-indolylmaleimides as a novel class of mutant isocitrate dehydrogenase-1 inhibitors: Design, synthesis, and biological evaluation
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A series of 3-(7-azainodyl)-4-indolylmaleimides was designed, synthesized, and evaluated for their isocitrate dehydrogenase 1 (IDH1)/R132H inhibitory activities. Many compounds such as 11a, 11c, 11e, 11g, and 11s exhibited favorable inhibitory effects on IDH1/R132H and were highly selective against the wild-type IDH1. Evaluation of the biological activities at the cellular level showed that compounds 11a, 11c, 11e, 11g, and 11s could effectively suppress the production of 2-hydroxyglutaric acid in U87MG cells expressing IDH1/R132H. Preliminary structure–activity relationship (SAR) and molecular modeling studies were discussed based on the experimental data obtained. These findings may provide new insights into the development of novel IDH1/R132H inhibitors.
- Hu, Yuanyuan,Gao, Anhui,Liao, Honghui,Zhang, Mengmeng,Xu, Gaoya,Gao, Lixin,Xu, Lei,Zhou, Yubo,Gao, Jianrong,Ye, Qing,Li, Jia
-
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- Synthesis of thiazole linked indolyl-3-glyoxylamide derivatives as tubulin polymerization inhibitors
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A series of thiazole linked indolyl-3-glyoxylamide derivatives were synthesized and evaluated for their in vitro cytotoxic activity against DU145 (prostate), PC-3 (prostate), A549 (lung) and HCT-15 (colon) cancer cell lines by employing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Among all the synthesized compounds, compound 13d displayed cytotoxicity of IC50 = 93 nM towards DU145 cancer cell line. The most active compound 13d was also tested on RWPE-1 cells and was found to be safe compared to the DU145 cells. The target compounds were also evaluated for their inhibition activity of tubulin polymerization. Further, the treatment of compound 13d on DU145 cells led to the inhibition of cell migration ability. The detailed studies such as acridine orange/ethidium Bromide (AO/EB), DAPI, annexin V-FITC/propidium iodide staining assay suggested that the compound 13d induced apoptosis in DU145 cells. The influence of the cytotoxic compound 13d on the cell cycle distribution was assessed on the DU145 cell line, exhibiting a cell cycle arrest at the G2/M phase. Moreover, the treatment with compound 13d caused collapse of mitochondrial membrane potential and elevated intracellular ROS levels in DU145 cells. The results from molecular modelling studies revealed that these compounds bind at the colchicine binding site of the tubulin. Thus, this new molecular scaffold could be a new lead for the development of anticancer agents that target tubulin.
- Guggilapu, Sravanthi Devi,Guntuku, Lalita,Reddy, T. Srinivasa,Nagarsenkar, Atulya,Sigalapalli, Dilep Kumar,Naidu,Bhargava, Suresh K.,Bathini, Nagendra Babu
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- Development of [18F]Maleimide-Based Glycogen Synthase Kinase-3β Ligands for Positron Emission Tomography Imaging
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Dysregulation of glycogen synthase kinase-3β (GSK-3β) is implicated in the pathogenesis of neurodegenerative and psychiatric disorders. Thus, development of GSK-3β radiotracers for positron emission tomography (PET) imaging is of paramount importance, because such a noninvasive imaging technique would allow better understanding of the link between the activity of GSK-3β and central nervous system disorders in living organisms, and it would enable early detection of the enzyme’s aberrant activity. Herein, we report the synthesis and biological evaluation of a series of fluorine-substituted maleimide derivatives that are high-affinity GSK-3β inhibitors. Radiosynthesis of a potential GSK-3β tracer [18F]10a is achieved. Preliminary in vivo PET imaging studies in rodents show moderate brain uptake, although no saturable binding was observed in the brain. Further refinement of the lead scaffold to develop potent [18F]-labeled GSK-3 radiotracers for PET imaging of the central nervous system is warranted.
- Hu, Kongzhen,Patnaik, Debasis,Collier, Thomas Lee,Lee, Katarzyna N.,Gao, Han,Swoyer, Matthew R.,Rotstein, Benjamin H.,Krishnan, Hema S.,Liang, Steven H.,Wang, Jin,Yan, Zhiqiang,Hooker, Jacob M.,Vasdev, Neil,Haggarty, Stephen J.,Ngai, Ming-Yu
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supporting information
p. 287 - 292
(2017/03/17)
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- Design and synthesis of bis(indolyl)ketohydrazide-hydrazones: Identification of potent and selective novel tubulin inhibitors
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A novel series of ketohydrazide-hydrazones as analogues of naturally occurring coscinamides has been synthesized and evaluated for their anticancer activity against five cancer cell lines. Of the twenty-synthesized ketohydrazide-hydrazones, compounds, 21c, 21f, 21g, 21k and 21o showed cytotoxic effects (less than 50% cell survival) against multiple cancer cell lines when tested at a final concentration of 10?μM. IC50 of three compounds 21f, 21k and 21o was determined to be less than 5?μM for all tested cancer cell lines. Compound 21k exhibited significant anticancer activity against MCF-7, MDA-MB-231, HCT-116 and JURKAT cancer cell lines with IC50 values of 0.8?μM, 0.50?μM, 0.15?μM, and 0.22?μM, respectively. Also, 21k was found to be more selectively cytotoxic against tumor cells when compared to normal cells. Preliminary mechanism of action studies indicated that the most active compound 21k induced caspase-dependent apoptosis in cells. 21k arrests cell cycle in G2/M phase by inhibiting of tubulin polymerization (IC50?=?0.6?μM).
- Tantak, Mukund P.,Klingler, Linus,Arun,Kumar, Anil,Sadana, Rachna,Kumar, Dalip
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p. 184 - 194
(2017/05/12)
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- An environmentally friendly protocol for oxidative halocyclization of tryptamine and tryptophol derivatives
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An environmentally friendly and efficient protocol (KX/oxone) for oxidative halocyclization of tryptamine/tryptophol derivatives was developed and demonstrated with 28 examples and concise total synthesis of cyclotryptamine alkaloid protubonines A and B. The distinct advantage of this protocol over all previous methods is that no organic byproduct is generated from a halogenating agent or oxidant, thus greatly reducing the environmental impact of halocyclization and facilitating the post-reaction purification.
- Xu, Jun,Tong, Rongbiao
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supporting information
p. 2952 - 2956
(2017/07/24)
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- Discovery of Topsentin Alkaloids and Their Derivatives as Novel Antiviral and Anti-phytopathogenic Fungus Agents
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Topsentin alkaloids and their derivatives were designed, synthesized, and characterized on the basis of NMR and mass spectroscopy. The antiviral activities against tobacco mosaic virus (TMV) and anti-phytopathogenic fungus activities of these alkaloids were evaluated for the first time. Alkaloids 1c, 1e, 2b, and 2d displayed significantly higher antiviral activities against TMV than Ribavirin, emerging as new lead compounds for anti-TMV research. Further fungicidal activity tests against 14 kinds of phytopathogenic fungi revealed that these alkaloids displayed broad-spectrum fungicidal activities. Topsentin derivative 2d with 4-5 mg/kg EC50 values against Sclerotinia sclerotiorum (Lib.), Rhizoctonia solani (Kuhn), and Botrytis cinerea (Pers.) emerged as a new lead compound for fungicidal research. Current studies provide support for the application of topsentin alkaloids as novel agrochemicals.
- Ji, Xiaofei,Wang, Ziwen,Dong, Ji,Liu, Yuxiu,Lu, Aidang,Wang, Qingmin
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p. 9143 - 9151
(2016/12/16)
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- Sequential one-pot synthesis of bis(indolyl)glyoxylamides: Evaluation of antibacterial and anticancer activities
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A series of bis(indolyl)glyoxylamides 10a-n has been designed and synthesized. In situ generated indole-3-glyoxalylchloride from the reaction of readily available indole 9 with oxalyl chloride was treated with tryptamine to produce bis(indolyl)glyoxylamides 10a-n in 82-93% yields. All the synthesized bis(indolyl)glyoxylamides were well characterized and tested for their antibacterial activity against Gram-positive and Gram-negative bacterial strains. Compounds 10d, 10g and 10i were found to display potent antibacterial activity against Gram-negative strain. Further, the cytotoxicity of bis(indolyl)glyoxylamides 10a-n were evaluated against a panel of human cancer cell lines. Of the screened analogues, compound 10f (IC50 = 22.34 μM; HeLa, 24.05 μM; PC-3, 21.13 μM; MDA-MB-231 and 29.94 μM; BxPC-3) was identified as the most potent analogue of the series. Exposure of PC-3 cells to either 10a or 10f resulted in increased levels of cleaved PARP1, indicating that bis(indolyl)glyoxylamides induce apoptosis in PC-3 cells. Most importantly, compounds 10d, 10g and 10i were completely ineffective in mammalian cells, suggesting that they target bacterial-specific targets and thus will not display any toxicity in host cells.
- Tantak, Mukund P.,Gupta, Vishakha,Nikhil, Kumar,Arun,Singh, Rajnish Prakash,Jha, Prabhat Nath,Shah, Kavita,Kumar, Dalip
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supporting information
p. 3167 - 3171
(2016/06/13)
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- EFFICIENT AND SCALABLE SYSTHESIS OF 2-(1'H-INDOLE-3'-CARBONYL)-THIAZOLE-4-CARBOXYLIC ACID METHYL ESTER AND ITS STRUCTURAL ANALOGS
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Methods of synthesizing 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) and structural analogs thereof. The methods include condensation reactions or condensation and oxidation reactions to form the thiazoline or thiazole moiety of ITE or its structural analogs.
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Page/Page column 19-20
(2016/06/01)
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- Synthesis and Anticancer Activity of 1-(1H -Indol-3-yl)-2-(4-diarylmethylpiperazine-1-yl)ethane-1,2-dione Derivatives
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Several new 1-(4-diarylmethylpiperazine-1-yl)-2-(1H-indol-3-yl)ethane-1,2-dione derivatives were synthesized by acylation of 1-diarylmethylpiperazine with 2-(1H-indol-3-yl)-2-oxoacetyl chloride. Their structures were confirmed by 1H NMR, IR, mass spectra, and elemental analysis. These compounds were further evaluated for their anticancer activity, and most of them were found to have moderate-to-potent antiproliferative activities against Hela, A-549, and ECA-109 cancer cell lines in vitro.
- Jiang, Jun-Rong,Xu, Feng,Wu, Han-Gui
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- Enantioselective Model Synthesis and Progress toward the Putative Structure of Yuremamine
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An enantioselective model synthesis of the 2,3-dihydro-1H-pyrrolo[1,2-a]indole core of the putative structure of yuremamine is reported in 39% overall yield and 96% ee over five steps. The model synthesis leverages enantioselective, rhodium-catalyzed hydroacylation of an N-vinylindole-2-carboxaldehyde as the key step in the installation of the stereochemical triad. An enantioselective synthesis of a densely functionalized dihydropyrroloindolone that maps onto the putative structure of yuremamine is demonstrated in 26% yield and 97% ee over eight steps.
- Ghosh, Avipsa,Bainbridge, David T.,Stanley, Levi M.
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p. 7945 - 7951
(2016/09/12)
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- Synthesis and biological activity of novel mono-indole and mono-benzofuran inhibitors of bacterial transcription initiation complex formation
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Our ongoing research focused on targeting transcription initiation in bacteria has resulted in synthesis of several classes of mono-indole and mono-benzofuran inhibitors that targeted the essential protein-protein interaction between RNA polymerase core and σ70/σA factors in bacteria. In this study, the reaction of indole-2-, indole-3-, indole-7- and benzofuran-2-glyoxyloyl chlorides with amines and hydrazines afforded a variety of glyoxyloylamides and glyoxyloylhydrazides. Similarly, condensation of 2- and 7-trichloroacetylindoles with amines and hydrazines delivered amides and hydrazides. The novel molecules were found to inhibit the RNA polymerase-σ70/σA interaction as measured by ELISA, and also inhibited the growth of both Gram-positive and Gram-negative bacteria in culture. Structure-activity relationship (SAR) studies of the mono-indole and mono-benzofuran inhibitors suggested that the hydrophilic-hydrophobic balance is an important determinant of biological activity.
- Mielczarek, Marcin,Thomas, Ruth V.,Ma, Cong,Kandemir, Hakan,Yang, Xiao,Bhadbhade, Mohan,Black, David Stc.,Griffith, Renate,Lewis, Peter J.,Kumar, Naresh
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p. 1763 - 1775
(2015/03/30)
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- Design, synthesis and characterization of indole based anion sensing receptors
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The design and synthesis of six new receptors (R1-R6) and their anion sensing properties through multiple channels are reported. These receptors are constructed in such a way that they possess indole groups as the binding sites and different acceptors units of varying electron acceptor strengths. Receptors R1, R3 and R5 could recognize fluoride ions visually and spectroscopically with high selectivity over other anions in DMF, which was demonstrated by a visual detection experiment and UV-Vis, fluorescence and 1H NMR spectral studies. The remaining three receptors (R2, R4 and R6) exhibited colour changes with both fluoride and cyanide ions. The binding constants for fluoride binding by these receptors were determined to be in the order of 104 to 106 M-1 and found to depend on the electron accepting property of the acceptor unit in the intra molecular charge transfer (ICT) transition existing with the indole donor units. 1H NMR titration experiments not only provide evidence for the existence of H-bonding interactions between the indolic N-H groups of these receptors and F-, but also offer key insight into the strengths of the receptor-anion complexes of stoichiometry 1:2. The higher fluoride binding ability of the receptor containing the naphthoquinone signalling unit has been interpreted in terms of the greater electron deficiency of the acceptor unit (quinone) and enhanced H-bond donating character of the indole N-H group. The results of the electrochemical and DFT computation studies corroborate well with the spectroscopic studies.
- Manivannan, Ramalingam,Satheshkumar, Angupillai,El-Mossalamy, El-Sayed H.,Al-Harbi, Laila M.,Kosa, Samia A.,Elango, Kuppanagounder P.
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p. 3936 - 3947
(2015/05/20)
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- Synthesis and biological evaluation of 3-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-4-(indol-3-yl)-maleimides as potent, selective GSK-3β inhibitors and neuroprotective agents
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A series of novel 3-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-4-(indol-3-yl)-maleimides were designed, prepared and evaluated for their GSK-3β inhibitory activities. Most compounds showed high potency to GSK-3β inhibition with high selectivity. Among them, compounds 7c, 7f, 7h, 7l and 7m significantly reduced GSK-3β substrate Tau phosphorylation at Ser396 in primary neurons, showing the inhibition of cellular GSK-3β. In the in vitro neuronal injury models, compounds 7c, 7f, 7h, 7l and 7m prevented neuronal death against glutamate, oxygen-glucose deprivation and nutrient serum deprivation which are associated with cerebral ischemic stroke. In the in vivo cerebral ischemia animal model, compound 7f reduced infarct size by 15% and improved the neurological deficit following focal cerebral ischemia. These findings may provide new insights into the development of novel GSK-3β inhibitors with potential neuroprotective activity.
- Ye, Qing,Mao, Weili,Zhou, Yubo,Xu, Lei,Li, Qiu,Gao, Yuanxue,Wang, Jing,Li, Chenhui,Xu, Yazhou,Xu, Yuan,Liao, Hong,Zhang, Luyong,Gao, Jianrong,Li, Jia,Pang, Tao
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p. 1179 - 1188
(2015/03/04)
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- Indole based peptidomimetics as anti-inflammatory and anti-hyperalgesic agents: Dual inhibition of 5-LOX and COX-2 enzymes
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The indoles bearing a tosyl group at N-1 and a dipeptide substituent at C-3 were screened for anti-inflammatory and anti-hyperalgesic activities. Some of the compounds made significant reduction in the dextran induced swelling and capsaicin induced pain in the albino mice. About 95% reversal in capsaicin induced pain occurred in the presence of 5 mg kg-1of compound 7b, 7d and 7h while diclofenac showed 90% reversal when its 10 mg kg-1 dose was used. In order to examine the mode of action of these compounds; COX-1, COX-2 and 5-LOX enzyme immunoassays were performed. The IC50 of compound 7b for COX-2 and 5-LOX were in the nM range: 5-LOX, IC50 Combining double low line 2.0 nM; COX-2, IC50 Combining double low line 6.3 nM, selectivity for COX-2 over COX-1 was 351. The interactions of the compounds with COX-2 and 5-LOX were supported by the physical parameters including Ki, Ka and δ G. The most potent compounds 7b, 7d and 7h showed no toxicity to the animals and were identified as the promising leads for anti-inflammatory drugs.
- Singh, Palwinder,Prasher, Parteek,Dhillon, Parvirti,Bhatti, Rajbir
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supporting information
p. 104 - 123
(2015/05/13)
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- A new synthesis of versatile indolyl-3-carbonylnitriles
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Abstract Indolyl-3-carbonylnitriles are compounds with demonstrated utility as intermediates in organic chemistry. However, their synthesis remains a challenge, requiring the use of toxic sources of cyanide, and often proceeding in low yields. Accordingly, presented here is a new synthesis of these versatile reactants, via dehydration of easily accessible α-oxoacetamides in generally high yields under simple reaction conditions.
- Veale, Clinton G.L.
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p. 5287 - 5290
(2015/08/26)
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- Synthesis and Evaluation of 3-(furo[2,3-b]pyridin-3-yl)-4-(1H-indol-3-yl)-maleimides as Novel GSK-3β Inhibitors and Anti-Ischemic Agents
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A series of novel 3-(furo[2,3-b]pyridin-3-yl)-4-(1H-indol-3-yl)-maleimides were designed, synthesized, and biologically evaluated for their GSK-3β inhibitory activities. Most compounds showed favorable inhibitory activities against GSK-3β protein. Among them, compounds 5n, 5o, and 5p significantly reduced GSK-3β substrate tau phosphorylation at Ser396 in primary neurons, indicating inhibition of cellular GSK-3β activity. In the in vitro neuronal injury models, compounds 5n, 5o, and 5p prevented neuronal death against glutamate, oxygen-glucose deprivation, and nutrient serum deprivation which are closely associated with cerebral ischemic stroke. In the in vivo cerebral ischemia animal model, compound 5o reduced infarct size by 10% and improved the neurological deficit. The results may provide new insights into the development of novel GSK-3β inhibitors with potential neuroprotective activity against brain ischemic stroke.
- Ye, Qing,Li, Qiu,Zhou, Yubo,Xu, Lei,Mao, Weili,Gao, Yuanxue,Li, Chenhui,Xu, Yuan,Xu, Yazhou,Liao, Hong,Zhang, Luyong,Gao, Jianrong,Li, Jia,Pang, Tao
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p. 746 - 752
(2015/03/30)
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- Dearomatization of tryptophols via a vanadium-catalyzed asymmetric epoxidation and ring-opening cascade
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An enantioselective epoxidation of tryptophols followed by an intramolecular epoxide opening reaction was realized by chiral vanadium catalysts derived from C2 symmetric bis-hydroxamic acid (BHA) ligands. 3a-Hydroxyfuroindoline derivatives with up to 89% yield and 90% ee were obtained under mild reaction conditions.
- Han, Long,Liu, Chuan,Zhang, Wei,Shi, Xiao-Xin,You, Shu-Li
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supporting information
p. 1231 - 1233
(2014/02/14)
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- Lead modification: Amino acid appended indoles as highly effective 5-LOX inhibitors
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N-1 tosyl indoles carrying amino acid as a part of C-3 substituent are identified with considerable 5-LOX inhibitory activities. On the basis of enzyme inhibitory activities and log P, it is found that these compounds are more suitable to use as ester prodrugs. In addition to the significant Ka and Ki for 5-LOX, advantageously the compounds under present investigation do not affect the viability of the cell. The experimental results were also supported by molecular docking of compounds in the active site of 5-LOX.
- Prasher, Parteek,Pooja,Singh, Palwinder
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supporting information
p. 1642 - 1648
(2014/03/21)
-
- Sulfur rich 2-mercaptobenzothiazole and 1,2,3-triazole conjugates as novel antitubercular agents
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A series of benzfused heterocyclic derivatives such as amide conjugates of 2-(benzo[d]thiazol-2-ylthio)acetic acid with aromatic/aliphatic/cyclic secondary amines (5a-5o & 8a-8m); 1,2,3-triazole conjugates of 2- mercaptobenzothiazoles and amide conjugates of indole-3-glyoxalic acid with cyclic secondary amines (14a-14g) have been synthesized and were screened for their antitubercular activity against Mycobacterium tuberculosis H37Rv strain by broth microdilution assay method. Compounds 8b, 8f, 8g and 8l inhibited the growth of the H37Rv strain at concentrations of 8 μg/mL. These compounds (8b, 8f, 8g and 8l) have been further identified as bactericidal and are completely killing the microbes at 32-64 μg/mL concentrations. Molecular docking studies of the active compounds reveal that these compounds are targeting DprE1 and may act as DprE1 inhibitors.
- Mir, Fauzia,Shafi, Syed,Zaman,Kalia, Nitin Pal,Rajput, Vikrant S.,Mulakayala, Chaitanya,Mulakayala, Naveen,Khan, Inshad A.,Alam
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p. 274 - 283
(2014/03/21)
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- Synthesis and biological activity of novel bis-indole inhibitors of bacterial transcription initiation complex formation
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The increasing resistance of bacteria against clinically approved antibiotics is resulting in an alarming decrease in therapeutic options for today's clinicians. We have targeted the essential interaction between bacterial RNA polymerase and σ70/σA for the development of lead molecules exhibiting a novel mechanism of antibacterial activity. Several classes of structurally related bis-indole inhibitors of bacterial transcription initiation complex formation were synthesized and their antimicrobial activities were evaluated. Condensation of indole-7- and indole-2-carbohydrazides with 7- and 2-trichloroacetylindoles or indole-7- and indole-2-glyoxyloyl chlorides resulted in the successful synthesis of 7,7′-, 2,2′-, 2,7′- and 3,2′-linked bis-indole derivatives with -CO-NH-NH-CO- and -CO-CO-NH-NH-CO- linkers. Indole-7-glyoxyloyl chlorides were reacted with hydrazine hydrate in different ratios to afford respective -CO-CO-NH-NH-CO-CO- bis-indole or hydrazide derivatives. The resulting compounds were found to be active against the β′-CH- σ70/σA2.2 interaction in ELISA assays and inhibited the growth of both Gram-positive and Gram-negative bacteria. Structure-activity relationship (SAR) studies were performed in order to identify the structural features of the synthesized inhibitors required for biological activity. This journal is the Partner Organisations 2014.
- Mielczarek, Marcins,Devakaram, Ruth V.,Ma, Cong,Yang, Xiao,Kandemir, Hakan,Purwono, Bambang,Black, David Stc.,Griffith, Renate,Lewis, Peter J.,Kumar, Naresh
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p. 2882 - 2894
(2014/05/06)
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- Alpha-ethyltryptamines as dual dopamine-serotonin releasers
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The dopamine (DA), serotonin (5-HT), and norepinephrine (NE) transporter releasing activity and serotonin-2A (5-HT2A) receptor agonist activity of a series of substituted tryptamines are reported. Three compounds, 7b, (+)-7d and 7f, were found to be potent dual DA/5-HT releasers and were >10-fold less potent as NE releasers. Additionally, these compounds had different activity profiles at the 5-HT2Areceptor. The unique combination of dual DA/5-HT releasing activity and 5-HT2Areceptor activity suggests that these compounds could represent a new class of neurotransmitter releasers with therapeutic potential.
- Blough, Bruce E.,Landavazo, Antonio,Partilla, John S.,Decker, Ann M.,Page, Kevin M.,Baumann, Michael H.,Rothman, Richard B.
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supporting information
p. 4754 - 4758
(2015/01/09)
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- Novel bis-indolic derivatives, their uses in particular as antibacterials
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The present invention relates to novel bis-indolic derivatives, processes for their preparation, and their potential use as new antibacterial drugs.
- -
-
Paragraph 0136
(2013/03/26)
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- BIS-INDOLIC DERIVATIVES, THEIR USES IN PARTICULAR AS ANTIBACTERIALS
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The present invention relates to novel bis-indolic derivatives, processes for their preparation, and their potential use as new antibacterial drugs.
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Page/Page column 23
(2013/03/26)
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- Dissecting metabolic puzzles through isotope feeding: A novel amino acid in the biosynthetic pathway of the cruciferous phytoalexins rapalexin A and isocyalexin A
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Understanding defence pathways of plants is crucial to develop disease-resistant agronomic crops, an important element of sustainable agriculture. For this reason, natural plant defenses such as phytoalexins, involved in protecting plants against microbial pathogens, have enormous biotechnological appeal. Crucifers are economically important plants, with worldwide impact as oilseeds, vegetables of great dietetic value and even nutraceuticals. Notably, the intermediates involved in the biosynthetic pathways of unique cruciferous phytoalexins such as rapalexin A and isocyalexin A remain unknown. Toward this end, using numerous perdeuterated compounds, we have established the potential precursors of these unique phytoalexins and propose for the first time their detailed biosynthetic pathway. This pathway involves a variety of intermediates and a novel amino acid as the central piece of this complex puzzle. This work has set the stage for the discovery of enzymes and genes of the biosynthetic pathway of cruciferous phytoalexins of unique scaffolds.
- Pedras, M. Soledade C.,Yaya, Estifanos E.
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p. 1149 - 1166
(2013/03/29)
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- Synthesis and biological evaluation of 3-benzisoxazolyl-4-indolylmaleimides as potent, selective inhibitors of glycogen synthase kinase-3β
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A series of novel 3-benzisoxazolyl-4-indolyl-maleimides were synthesized and evaluated for their GSK-3β inhibitory activity. Most compounds exhibited high inhibitory potency towards GSK-3β. Among them, compound 7j with an IC50 value of 0.73 nM was the most promising GSK-3β inhibitor. Preliminary structure-activity relationships were examined and showed that different substituents on the indole ring and N1-position of the indole ring had varying degrees of influence on the GSK-3β inhibitory potency. Compounds 7c, 7f, 7j-l and 7o-q could obviously reduce Aβ-induced Tau hyperphosphorylation by inhibiting GSK-3β in a cell-based functional assay.
- Ye, Qing,Li, Meng,Zhou, Yubo,Pang, Tao,Xu, Lei,Cao, Jiayi,Han, Liang,Li, Yujin,Wang, Weisi,Gao, Jianrong,Li, Jia
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p. 5498 - 5516
(2013/06/27)
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- Methods of Making and Using Thioxothiazolidine and Rhodanine Derivatives as HIV-1 and JSP-1 Inhibitors
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The present invention provides methods of making and using 5-(2-(indol-3-yl)-2-oxoethylidene)-3-phenyl-2-thioxothiazolidin-4-one derivatives having HIV-1 or JSP-1 inhibitory activity.
- -
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Paragraph 0056; 0049
(2013/10/07)
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