- A new cytotoxic cholestane bisdesmoside from Ornithogalum saundersiae bulbs
-
Bioassay-guided fractionation of the MeOH extract of Ornithogalum saundersiae bulbs led to the isolation of a new cholestane bisdcsmoside with potent cytotoxic activities toward leukemia HL-60 and MOLT-4 cells. The structure was deduced mainly from spectroscopic information.
- Mimaki, Yoshihiro,Kuroda, Minpei,Kameyama, Aiko,Sashida, Yutaka,Hirano, Toshihiko,Oka, Kitaro,Koike, Kazuo,Nikaido, Tamotsu
-
-
Read Online
- Phyllanemblinins A-F, new ellagitannins from Phyllanthus emblica
-
Six new ellagitannins, phyllanemblinins A-F (1-6), were isolated from Phyllanthus emblica, along with 30 known tannins and related compounds. Their structures were determined by spectral and chemical methods. Phyllanemblinins A (1) and B (2) were confirme
- Zhang, Ying-Jun,Abe, Tomomi,Tanaka, Takashi,Yang, Chong-Ren,Kouno, Isao
-
-
Read Online
- Design, synthesis and biological evaluation of a novel tubulin inhibitor 7a3 targeting the colchicine binding site
-
Tubulin inhibitors that target the colchicine binding site continue to emerge as promising anticancer agents. In this study, based on the anti-proliferative activities, a novel tubulin inhibitor 7a3 targeting the colchicine binding site was designed, synthesized, and optimized from a series of novel cis-restricted pyrazole analogues of combretastatin A-4. The structure-activity relationships (SARs) of these newly synthesized compounds are summarized indicating that the methyl substituent at the N1 position and deamination were significantly important for the anti-proliferative efficacy. The optimized compound 7a3 exhibited the ability to arrest the cell cycle in the G2/M phase, induce cell apoptosis, and inhibit cell migration in tumour cells. The results of the immunofluorescence analysis using confocal microscopy and the tubulin polymerization assay revealed that tubulin assembly was disrupted by 7a3 in vitro. Furthermore, the targeting identification of 7a3 was illuminated by solving the crystal structure of 7a3 in complex with tubulin at a resolution of 3.2 ? (PDB code 5Z4U), which confirmed the result of molecular docking and further demonstrated that 7a3 binds to the site of colchicine. Moreover, the pharmacokinetic analysis in mouse plasma showed that 7a3 rapidly reached a peak concentration at 0.25 h after intraperitoneal administration, and the T1/2, Cmax, and AUC0-inf were 1.67 ± 0.28 h, 882 ± 71 ng mL-1, and 1166 ± 129 h ng·mL-1, respectively, after a single-dose administration analysed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). In addition, the in vivo study indicated that 7a3 significantly inhibited the tumour growth of the SK-OV-3 xenograft in a nude mouse model. In conclusion, our study proved 7a3 to be a potential microtubule-targeting drug for cancer therapy. The SARs and mechanism of action studies of 7a3 based on the X-ray co-crystal structure provided insights into the next-generation tubulin inhibitors for cancer therapy.
- Lai, Qinhuai,Wang, Yuxi,Wang, Ruixue,Lai, Weirong,Tang, Liangze,Tao, Yiran,Liu, Yu,Zhang, Ruirui,Huang, Luyi,Xiang, Haotian,Zeng, Shaoxue,Gou, Lantu,Chen, Hao,Yao, Yuqin,Yang, Jinliang
-
-
Read Online
- PUNICAFOLIN, AN ELLAGITANNIN FROM THE LEAVES OF PUNICA GRANATUM
-
A new ellagitannin, punicafolin has been isolated from the leaves of Punica granatum and characterized by physicochemical data and spectral evidence as 1,2,4-tri-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-β-D-glucose.The occurrence in the leaves of the known tannins, granatins A and B, corilagin, strictinin, 1,2,4,6-tetra-O-galloyl-β-D-glucose and 1,2,3,4,6-penta-O-galloyl-β-D-glucose has also been demonstrated.Key Word Index -Punica granatum; Punicaceae; pomegranate; punicafolin; ellagitannin; gallotannin.
- Tanaka, Takashi,Nonaka, Gen-Ichiro,Nishioka, Itsuo
-
-
Read Online
- Biologically active bergenin derivatives from bergenia stracheyi
-
New bergenin derivatives, bergecins A and B (1 and 2, resp.), have been isolated from the AcOEt-soluble fraction of Bergenia stracheyi, along with bergenin (3), and their structures were elucidated on the basis of 1H- and 13C-NMR spectra, and by COSY, HMQC, and HMBC experiments. Compound 2 showed potent inhibitory potential against the enzyme lipoxygenase, while 1 was moderately active. On the other hand, both compounds exhibited significant antioxidant activities in 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay. Copyright
- Siddiq, Farah,Fatima, Itrat,Malik, Abdul,Afza, Nighat,Iqbal, Lubna,Lateef, Mehreen,Hameed, Saira,Khan, Sher Wali
-
-
Read Online
- Synthesis of 2,3-dimethoxy-5-methyl-1,4-benzoquinone: A key fragment in coenzyme-q series
-
Preparation of the title compound by a reaction sequence starting from gallic acid present in mango kernel is described.
- Chida,Vani,Chandrasekharam,Srinivasan,Singh
-
-
Read Online
- Structure and biogenesis of jolkinin, a highly oxygenated ellagitannin from Euphorbia jolkinii
-
A new ellagitannin, jolkinin (2), was isolated from the fresh whole plant of Euphorbia jolkinii, and its structure, including absolute configuration, was determined on the basis of spectroscopic and chemical evidence. A highly oxygenated acyl group with unique hexacyclic structure is attached to the 2,4-positions of 1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-β-D- glucopyranose. The structural similarity to elaeocarpusin (4) suggests that jolkinin is produced by a condensation reaction between ascorbic acid and geraniin (1), the dominant ellagitannin in this plant, which contains a dehydrohexahydroxydiphenoyl group. A plausible mechanism for jolkinin formation is also proposed.
- Lee, Seung-Ho,Tanaka, Takashi,Nonaka, Gen-Ichiro,Nishioka, Itsuo
-
-
Read Online
- Three novel C-glycosidic ellagitannins, Rhoipteleanins H, I, and J, from Rhoiptelea chiliantha
-
Three novel C-glycosidic ellagitannins named rhoipteleanins H (1), I (2), and J (3) were isolated from the fruits and bark of Rhoiptelea chiliantha Diels et Hand.-Mazz. (Rhoipteleaceae), and the structures were elucidated on the basis of detailed spectroscopic analysis and chemical evidence. Rhoipteleanin H possesses a unique cyclopentenone carboxyl moiety, which is probably formed by oxidation and subsequent rearrangement of an aromatic ring of a usual C-glycosidic ellagitannin. Rhoipteleanin I is the first ellagitannin having a hydroxynaphthalene glucoside moiety. Rhoipteleanin J is a dimeric ellagitannin generated by dehydrative coupling between two molecules of a monomeric C-glycosidic ellagitannin and subsequent oxidation of an aromatic ring. From a chemotaxonomic viewpoint, presence of these characteristic ellagitannins in this plant provides a further support for the establishment of the order Rhoipteleales comprising Rhoipteleaceae as the only family.
- Jiang, Zhi-Hong,Tanaka, Takashi,Kouno, Isao
-
-
Read Online
- Design and synthesis of novel parabanic acid derivatives as anticonvulsants
-
In this work a set of novel derivatives of parabanic acid 9a-d, 12a-d and 13a-d was synthesized and their anticonvulsant potential was evaluated. All the compounds under investigation exhibited anticonvulsant activity in both scPTZ and MES tests. In phase II anticonvulsant study, the trimethoxy phenyl derivative 9a evoked the highest potency among the tested compounds in scPTZ test. It displayed 1.72- and 17.05-folds activity more than the standard drugs phenobarbital and ethosuximide, respectively. In addition, the margin of safety for compound 9a is better than that of the reference antiepileptic drug ethosuximide. Also, compound 9a was devoid of hepatotoxicity indicated by measurements of serum level of ALT, AST, ALP, albumin and total protein. Furthermore, treatment with compound 9a significantly increased the GABA brain level by 2.56-folds compared to the control value. Additionally, molecular docking was performed on the active site of GABA-AT to clarify the interactions of the most potent compound 9a with the enzyme. In MES test, compound 12a exhibited the most potent activity against electric stimuli-induced seizures with the lowest ED50 = 13.7 mg/kg and protective index >36.5. Both candidates 9a and 12a could be a good starting point to develop new molecules as novel antiepileptic drugs.
- Aboutabl, Mona Elsayed,Hassan, Rasha Mohamed,El-Azzouny, Aida Abdel-Sattar,Aboul-Enein, Mohamed Nabil,Abd-Allah, Walaa Hamada
-
-
Read Online
- Synthesis, characterization (theoretical and biological study) of some transition metal complexes with new schiff base derived from 1,2,4-triazole
-
The present work involves, new Schiff base of (E)-2-(((3-mercapto-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazol-4-yl)imino)methyl)phenol (L2) has been synthesized by condensation reaction of 4-amino-5-(3,4,5 trimethoxy phenyl)-4H-1,2,4-triazole-3-thiol with 2-hydroxybenzaldehyde. The new Schiff base (L2) used as a ligand to synthesize a new complex with Co(II), Ni(II), Cu(II), Pd(II), and Cd(II) metal ions by 1:1 (Metal: ligand) ratio. New ligand and their complexes have been exanimated and confirmed by fourier-transform infrared (FT-IR), ultraviolet-visible (UV-visible), proton nuclear magnetic resonance (1HNMR), carbon13 nuclear magnetic resonance (13CNMR), microelement analysis (CHNS), thermal analysis (TG-DSC), atomic absorption flame (AAF), conductivity and magnetic susceptibility. The results obtained from spectra, elemental analyses and thermal analyses (TG-DSC) and compare by density functional theory (DFT) and TD-DFT calculations were screened for some selected complexes and the observed data indicated their stability and the expected chemical formula, Pd(II) were square planner, whereas the Cu(II), Co(II), Ni(II) octahedral, and Cd(II) were tetrahedral geometry . Furthermore, the antibacterial and antifungal activity was screened for the DMSO solution concerning the Schiff base (L2) and its complexes (20 μg/ml) against two kinds of gram; (Staphylococcus aureas and Bacillus subtilis) positive and two negative bacteria; (Esherichia coli and Burkholderia) and against (Candida albican) fungi. The results obtained from diffusion method confirmed the greater activity of Pd(II) and Cd(II) complexes whereas the Co(II),Cu(II) and Ni(II) complexes showed medium activity compared with the low inhibition zones of the free Schiff base of 1, 2, 4- triazole derivative.
- AL-Jibouri, Mahmoud Najim,Jawad, Waleed A.,Balakit, Asim A.,Obies, Mohammed
-
p. 5229 - 5241
(2021/08/31)
-
- Antibacterial and Antiviral Activities of 1,3,4-Oxadiazole Thioether 4H-Chromen-4-one Derivatives
-
Various 1,3,4-oxadiazole thioether 4H-chromen-4-one derivatives were conceived. The title compounds demonstrated striking inhibitory effects againstXac,Psa, andXoo. EC50data exhibited that A8 (19.7 μg/mL) had better antibacterial activity againstXoothan myricetin, BT, and TC. Simultaneously, the mechanism of action of A8 had been verified by SEM. The results of anti-tobacco mosaic virus indicated that A9 had the bestin vivoantiviral effect compared with ningnanmycin. From the data of MST, it could be seen that A9 (0.003 ± 0.001 μmol/L) exhibited a strong binding capacity, which was far superior to ningnanmycin (2.726 ± 1.301 μmol/L). This study shows that the 1,3,4-oxadiazole thioether 4H-chromen-4-one derivatives may become agricultural drugs with great potential.
- Cao, Xiao,Liu, Fang,Liu, Liwei,Liu, Tingting,Peng, Feng,Wang, Qifan,Xie, Chengwei,Xue, Wei,Yang, Jinsong
-
p. 11085 - 11094
(2021/10/01)
-
- Polyhydroxybenzoic acid derivatives as potential new antimalarial agents
-
With more than 200 million cases and 400,000 related deaths, malaria remains one of the deadliest infectious diseases of 2021. Unfortunately, despite the availability of efficient treatments, we have observed an increase in people infected with malaria since 2015 (from 211 million in 2015 to 229 million in 2019). This trend could partially be due to the development of resistance to all the current drugs. Therefore, there is an urgent need for new alternatives. We have, thus, selected common natural scaffolds, polyhydroxybenzoic acids, and synthesized a library of derivatives to better understand the structure–activity relationships explaining their antiplasmodial effect. Only gallic acid derivatives showed a noticeable potential for further developments. Indeed, they showed a selective inhibitory effect on Plasmodium (IC50 ~20 μM, SI > 5) often associated with interesting water solubility. Moreover, this has confirmed the critical importance of free phenolic functions (pyrogallol moiety) for the antimalarial effect. Methyl 4-benzoxy-3,5-dihydroxybenzoate (39) has, for the first time, been recognized as a potential lead for future research because of its marked inhibitory activity against Plasmodium falciparum and its significant hydrosolubility (3.72 mM).
- Degotte, Gilles,Francotte, Pierre,Pirotte, Bernard,Frédérich, Michel
-
-
- Tubulin inhibitors: Discovery of a new scaffold targeting extra-binding residues within the colchicine site through anchoring substituents properly adapted to their pocket by a semi-flexible linker
-
Bis-hydrazides 13a-h were designed and synthesized as potential tubulin inhibitors selectively targeting the colchicine site between α- and β-tubulin subunits. The newly designed ring-B substituents were assisted at their ends by ‘anchor groups’ which are expected to exert binding interaction(s) with new additional amino acid residues in the colchicine site (beyond those amino acids previously reported to interact with reference inhibitors as CA-4 and colchicine). Conformational flexibility of bis-hydrazide linker assisted these ‘extra-binding’ properties through reliving ligands’ strains in the final ligand-receptor complexes. Compound 13f displayed the most promising computational and biological study results in the series: MM/GBSA binding energy of ?62.362 kcal/mol (extra-binding to Arg α:221, Thr β:353 & Lys β:254); 34% NCI-H522 cells’ death (at 10 μM), IC50 = 0.073 μM (MTT assay); significant cell cycle arrest at G2/M phase; 11.6% preG1 apoptosis induction and 83.1% in vitro tubulin inhibition (at concentration = IC50). Future researchers in bis-hydrazide tubulin inhibitors are advised to consider the 2-chloro-N-(4-substituted-phenyl)acetamide derivatives as compound 13f due to extra-binding properties of their ring B.
- AbdelHafez, El-Shimaa M. N.,Abdelhamid, Dalia,Aly, Omar M.,Maklad, Raed M.
-
-
- 6,7-Benzotropolone Syntheses Based on Ring-Closing Metatheses and Four-Electron Oxidations
-
Four homoallyl ortho-vinylaryl ketones (10a-d) – 1,8-dienes of sorts – were prepared by several approaches. In the presence of 1–2 mol-% Grubbs-II catalyst, they ring-closed to give 6,7-dihydrobenzocyclohepten-5-ones (11a-d) in 90–96 % yield. With SeO2 the parent compound (11a) delivered benzocyclohepten-5-one (13a) and/or selenium-containing compounds (18–22) but no more than traces of 6,7-benzotropolone (5a). However, 5a was accessible from compound 11a via the sodium enolate and allowing it to react with a stream of oxygen (43 % yield). The sodium enolates of the substituted 6,7-dihydrobenzocyclohepten-5-ones 11b–d and oxygen underwent analogous 4-electron oxidations. This furnished the substituted 6,7-benzotropolones 11b-d. In contrast, the corresponding lithium enolates were inert towards oxygen. The 6,7-dihydrobenzocyclohepten-5-one 11d was also accessed differently, namely by a Grubbs-II catalyst-mediated RCM/C=C migration tandem reaction of the allyl ortho-allylaryl ketone 73 – another 1,8-diene of sorts (90 % yield).
- Brückner, Reinhard,Fernandes, Manuel A.,Gemander, Manuel,Green, Ivan R.,Kreibich, Michael,Peter, David,Yadav, Dharmendra B.,de Koning, Charles B.,van Otterlo, Willem A. L.
-
-
- Fluorinated benzylidene indanone exhibits antiproliferative activity through modulation of microtubule dynamics and antiangiogenic activity
-
The application of fluorine in drug design has been understood significantly by the medicinal chemists in recent years. Modulation of tubulin-microtubule dynamics is one of the most effective targets for cancer chemotherapeutics. A logically designed and identified lead compound, fluorinated benzylidene indanone 1 has been extensively evaluated for cancer pharmacology. It occupied colchicine binding pocket acting as microtubule destabilizer and induced a G2/M phase arrest in MCF-7 cells. Compound 1 exerted an antiangiogenic effect in MCF-7 cells by down-regulating Vascular Endothelial Growth Factor (VEGF) and Hypoxia Inducible Factor-α (HIF-α). In in-vivo efficacy in C3H/Jax mice mammary carcinoma model, benzylidene indanone 1 reduced tumour volumes by 48.2%. Further in acute oral toxicity studies compound 1 was well tolerated and safe up to 1000 mg/kg dose in Swiss albino mice. The fluorinated benzylidene indanone 1, a new chemical entity (NCE) can further be optimized for better efficacy against breast adenocarcinoma.1
- Chanda, Debabrata,Fatima, Eram,Fatima, Kaneez,Khan, Feroz,Luqman, Suaib,Negi, Arvind S.,Shanker, Karuna,Shukla, Aparna,Singh, Aastha,Singh, Arjun,Srivastava, Ankita
-
-
- Cobalt Nanoparticles-Catalyzed Widely Applicable Successive C?C Bond Cleavage in Alcohols to Access Esters
-
Selective cleavage and functionalization of C?C bonds have important applications in organic synthesis and biomass utilization. However, functionalization of C?C bonds by controlled cleavage remains difficult and challenging because they are inert. Herein, we describe an unprecedented efficient protocol for the breaking of successive C?C bonds in alcohols to form esters with one or multiple carbon atoms less using heterogeneous cobalt nanoparticles as catalyst with dioxygen as the oxidant. A wide range of alcohols including inactive long-chain alkyl aryl alcohols undergo smoothly successive cleavage of adjacent ?(C?C)n? bonds to afford the corresponding esters. The catalyst was used for seven times without any decrease in activity. Characterization and control experiments disclose that cobalt nanoparticles are responsible for the successive cleavage of C?C bonds to achieve excellent catalytic activity, while the presence of Co-Nx has just the opposite effect. Preliminary mechanistic studies reveal that a tandem sequence reaction is involved in this process.
- Dai, Wen,Gao, Shuang,Li, Guosong,Luo, Huihui,Lv, Ying,Shang, Sensen,Wang, Lianyue
-
supporting information
p. 19268 - 19274
(2020/08/26)
-
- New composition for improving skin conditions
-
The present invention relates to a composition for improving skin condition which comprises a derivative of a compound represented by chemical formula (I) or a pharmacologically acceptable salt thereof. In the chemical formula (I), X is hydrogen or methoxy, and R is a C1 to C20 linear or branched alkyl group.COPYRIGHT KIPO 2020
- -
-
Paragraph 0078-0080
(2020/07/30)
-
- Ni-catalyzed direct alcoholysis of N-acylpyrrole-type tertiary amides under mild conditions
-
N-Acylpyrrole-type amides are a class of versatile building blocks in asymmetric synthesis. We report that by employing Ni(COD)2/2,2′-bipyridine (5 mol%) catalytic system, the direct, catalytic alcoholysis of N-acylpyrrole-type aromatic and aliphatic amides with both primary and secondary alcohols can be achieved efficiently under very mild conditions (rt, 1 h) even at gram scale. By increasing the catalyst loading to 10 mol%, prolonging reaction time (18 h), and/or elevating reaction temperature to 50 °C/80 °C, the reaction could be extended to both complex and hindered N-acylpyrroles as well as to N-acylpyrazoles, Nacylindoles, and to other (functionalized) primary and secondary alcohols. In all cases, only 1.5 equiv. of alcohol were used. The value of the method has been demonstrated by the racemization-free, catalytic alcoholysis of chiral amides yielded from other asymmetric methodologies.
- Chen, Hang,Chen, Dong-Huang,Huang, Pei-Qiang
-
p. 370 - 376
(2020/03/03)
-
- Discovery and optimization of 3,4,5-trimethoxyphenyl substituted triazolylthioacetamides as potent tubulin polymerization inhibitors
-
Based on our previous research, three series of new triazolylthioacetamides possessing 3,4,5-trimethoxyphenyl moiety were synthesized, and evaluated for antiproliferative activities and inhibition of tubulin polymerization. The most promising compounds 8b and 8j demonstrated more significant antiproliferative activities against MCF-7, HeLa, and HT-29 cell lines than our lead compound 6. Moreover, analogues 8f, 8j, and 8o manifested more potent antiproliferative activities against HeLa cell line with IC50 values of 0.04, 0.05 and 0.16 μM, respectively, representing 100-, 82-, and 25-fold improvements of the activity compared to compound 6. Furthermore, the representative compound, 8j, was found to induce significant cell cycle arrest at the G2/M phase in HeLa cell lines via a concentration-dependent manner. Meanwhile, compound 8b exhibited the most potent tubulin polymerization inhibitory activity with an IC50 value of 5.9 μM, which was almost as active as that of CA-4 (IC50 = 4.2 μM). Additionally, molecular docking analysis suggested that 8b formed stable interactions in the colchicine-binding site of tubulin.
- Yang, Fang,He, Cai-Ping,Diao, Peng-Cheng,Hong, Kwon Ho,Rao, Jin-Jun,Zhao, Pei-Liang
-
-
- Synthesis and antifungal activity of novel 1,2,4-triazole derivatives containing an amide moiety
-
A series of novel 1,2,4-triazol derivatives containing an amide moiety were synthesized and their antifungal activities were evaluated. The results indicated that some of the target compounds possessed good antifungal activities. Among them, compounds 6a, 6g, 6k, and 6m showed excellent antifungal activities against Botrytis cinerea, with an inhibition rate of 91.8%, 90.1%, 93.6%, and 91.2% at a concentration of 50 μg/mL, which were superior to that of Pyrimethanil (82.8%). Meanwhile, compound 6b showed better antifungal activity against Phompsis sp, with an inhibition rate of 92.4%, in comparison with that of Pyrimethanil (85.1%).
- Du, Hai-Tang,Fei, Qiang,Jiang, Yang-Ming,Wu, Wen-Neng,Yang, Mao-Fa
-
-
- Combretastatin A4 analogue containing cyanoethylene joining chain and application in preparing antitumor drugs
-
The invention a Combretastatin A4 analogue containing a cyanoethylene joining chain and an application in preparing antitumor drugs, which relates to the field of a medicinal compound. A structural formula (I-IV) is shown as the specification, an anticancer candidate compound which has strong inhibitory activity against cancer cells and is not toxic to normal cells is currently lacked, for the reason, the method prepares 19 I-IV series compounds, and the para and meta positions of the B ring (benzene ring) introduce various alkyl groups, alkoxy groups or amino substituents or replace the B ring (benzene ring) with various heterocyclic rings. In the I-series compound, when the para position of the B ring (benzene ring) is substituted with an ethyl group, an isopropyl group, a dimethylaminogroup or a diethylamino group, the proliferation resistance of the cancer cells is very strong, and toxicity is weak for the L-02 normal cells, a selective anticancer activity coefficient (an IC50 value ratio of L-02 normal cells to cancer cells) can even exceed 10,000, and the four compounds have the potential to be developed into safe and highly effective anticancer drugs.
- -
-
Paragraph 0044; 0045; 0046; 0047
(2019/03/15)
-
- Method for preparing carboxylic ester by alcohol direct oxidation esterification method
-
The invention discloses a method for preparing a carboxylic ester by an alcohol direct oxidation esterification method. The method comprises the following steps: taking an aromatic alcohol compound ora saturated linear aliphatic alcohol as a reaction substrate, taking an Au-Co composite particle carrier as a catalyst, adding a low catalytic amount of alkali, reacting for 0.5-15 h in a methanol solvent at the temperature of 25-150 DEG C in air or oxygen or a mixed atmosphere of the air or the oxygen, and performing aftertreatment to obtain a target product carboxylic ester. According to the preparation method disclosed by the invention, the process steps are reduced, conditions are mild, catalyst consumption is less, atom economy is high, the method is simple to operate, the application range of the substrate is wide, and industrial practicability is achieved.
- -
-
Paragraph 0058; 0059
(2019/06/30)
-
- Pd-Colloids-Catalyzed/Ag2O-Oxidized General and Selective Esterification of Benzylic Alcohols
-
Palladium colloids obtained from the degradation of Hermann–Beller palladacycle proved to be an efficient catalytic system in combination with silver oxide as a selective oxidant for the oxidative esterification of differently substituted benzyl alcohols in MeOH as solvent. Excellent reactivity exhibited by the catalytic system also allowed the alcoholic coupling partner to be changed from MeOH to a wide range of alcohols having diverse functionalities. The mildness of the developed protocol also made it possible to employ propargyl alcohol as the coupling partner without any observation of any interference of the terminal alkyne. Selective oxidative coupling of a primary alcoholic functional group over secondary in the case of glycols and glycerols was also made possible using the developed catalyst system. To test the relevancy of Pd/Ag combined catalysis mixed Pd/Ag colloids were synthesized, characterized by TEM, XRD and XPS and applied to oxidative-esterification successfully.
- Sable, Vaibhav,Shah, Jagrut,Sharma, Anuja,Kapdi, Anant R.
-
supporting information
p. 2639 - 2647
(2019/07/08)
-
- Microtubule inhibitor as well as preparation method and application thereof
-
The invention relates to a microtubule inhibitor as well as a preparation method and application thereof, belongs to the field of chemical medicines and aims to solve the problem that the biological activity is rapidly reduced because the existing microtubule inhibitor CA-4 cisoid conformation is easily transformed into trans-conformation. The technical scheme provides a compound expressed by a formula I as well as pharmaceutically acceptable salts or crystals thereof. Experiment results show that the compound shows extremely strong in-vitro anti-proliferation activity in tumor cells such as ovarian cancer cells, cervical cancer cells, non-small cell lung cancer cells, colon cancer cells and breast cancer cells, can obviously inhibit the tumor progression in the body, and is high in safety; the formula I is as shown in the description.
- -
-
Paragraph 0141; 0142
(2018/09/11)
-
- Synthesis and antitumor activity of novel 6,7,8-trimethoxy N-aryl-substituted-4-aminoquinazoline derivatives
-
A series of 6,7,8-trimethoxy N-aryl-substituted-4-aminoquinazoline derivatives were synthesized as epidermal growth factor receptor (EGFR) inhibitors, and their antitumor activities were assessed in the gastric cancer cell line SGC7901 using MTT assay. All compounds of Tg1–14 were found to inhibit SGC7901 cell proliferation, and compound Tg11 (IC50 = 0.434 μM) was found to be slightly more effective against SGC7901 cells than epirubicin (IC50 = 5.16 μM). This suggests that compound Tg11 can be used as a new substitution structure to develop more efficacious antitumor agents. Western blot analysis showed that treatment with Tg11 (40 μM for 30 min) resulted in near complete inhibition of EGF-induced ERK1/2 phosphorylation, indicating that its anti-proliferative effect is largely associated with inhibition of ERK1/2 activation. These data imply that Tg11 is a potential anticancer agent capable of inhibiting cell proliferation.
- Liu, Fang,Huai, Ziyou,Xia, Guotai,Song, Liuping,Li, Sha,Xu, Yulan,Hong, Kangjun,Yao, Mingyue,Liu, Gang,Huang, Yinjiu
-
supporting information
p. 2561 - 2565
(2018/06/20)
-
- Synthesis and cytotoxic activities of hexyl-esters derivatives of gallic acid against MCF-7 cell line
-
Gallic acid is found in many plants, fruits, and foods where the anti-cancer activity is found. However, gallic acid has a problem on the high polarity and low bio availability. So, it takes molecular modifications in order to increase its lipophilicity, which is expected to increase bio availability and cytotoxic activity of gallic acid. Hexyl esters derivatives of gallic acid were synthesized and characterized by spectrometer 1H-NMR, 13C-NMR, mass spectrometry and infrared spectrophotometer (FTIR). All compounds were then evaluated for cytotoxic activity on MCF-7 cell line using MTT method. Compound cis-2′-hexenyl-3,4,5-trimethoxygallate (19) had the lowest IC50 value compared with gallic acid and other derivatives hexyl esters. IC50 value of cis-2′-hexenyl-3,4,5-trimethoxygallate (19) is 14.48 μg/ml. Compound (19) also has approached with IC50 values of gossypol as a positive control. Compound (19) is a potential compound to inhibit growth of MCF-7 cell line.
- Paramita, Rafika Indah,Arsianti, Ade,Radji, Maksum
-
p. 295 - 300
(2018/03/21)
-
- Synthesis and in vitro antimalarial activity of alkyl esters of gallate as a growth inhibitor of plasmodium falciparum
-
This study is aimed to synthesize alkyl esters gallate and determine its in vitro antimalarial activity against parasite Plasmodium falciparum. Fourteen compounds of alkyl esters gallate were synthesized by esterification of the carboxyl group of gallic acid with a series of alkyl alcohols, as well as methoxylation of the hydroxy groups on the aromatic ring of gallic acid. Antimalarial activity of the synthesized alkyl esters gallate were expressed by IC50 value, with gallic acid as an original compound and artemisin as a positive control. Compared to gallic acid, eleven synthesized compounds of alkyl esters gallate, have a greater antimalarial activity against Plasmodium falciparum. On the other hand, three compounds, that are propyl gallate, butyl gallate and trimethoxy methyl gallate, showed a lower antimalarial activity. Moreover, compared to gallic acid (IC50: 194.86 mM) and artemisin (IC50: 0.5 mM), two synthesized compounds of alkyl gallates, namely methyl gallate and hexyl gallate exhibited the stronger antimalarial activity against Plasmodium falciparum, with IC50 value of 0.03 mM and 0.11 mM, respectively. Our result clearly demonstrated that methyl gallate and hexyl gallate as a promising candidate for the new antimalarial agents.
- Arsianti, Ade,Astuty, Hendri,Fadilah,Simadibrata, Daniel Martin,Adyasa, Zoya Marie,Amartya, Daniel,Bahtiar, Anton,Tanimoto, Hiroki,Kakiuchi, Kiyomi
-
p. 655 - 662
(2018/05/28)
-
- Preparation and uses of combretastatin A4 analogs containing cyano and halogen
-
The present invention provides preparation and uses of combretastatin A4 analogs containing cyano and halogen, and relates to the field of medicinal compounds, wherein the structure of the combretastatin A4 analog is represented by the following formula defined in the specification. In the prior art, the selective anticancer activity compounds with characteristics of strong inhibition activity oncancer cells and no toxicity to normal cells are necessary to the generation of novel anticancer drugs while the compounds are absent. According to the present invention, based on the requirements inthe prior art, 11 series I combretastatin A4 analogs with fluorine, chlorine, bromine or trifluoromethyl at the ortho position, meta position or para position of the B ring, and 7 series II analogs are synthesized; in the series I compounds, when the para position of the B ring is substituted by fluorine, chlorine, bromine or trifluoromethyl, the good selective anticancer activity can be achieved,and the toxicity to L-02 normal cells is weak; when the para position is substituted by fluorine, chlorine or bromine, a ratio of the IC50 value in AGS cancer cells to the IC50 value in L-02 normal cells is greater than 100; when the para position is substituted by trifluoromethyl, a ratio of the IC50 value in MGC-803 cancer cells to the IC50 value in L-02 normal cells is greater than 100; and the selective anticancer activity of the four compounds is good.
- -
-
Paragraph 0033; 0034; 0035
(2018/09/29)
-
- Synthesis and characterisation of (Z)-styrylbenzene derivatives as potential selective anticancer agents
-
To identify anticancer agents with high potency and low toxicity, a series of (Z)-styrylbenzene derivatives were synthesised and evaluated for anticancer activities using a panel of nine cancer cell lines and two noncancerous cell lines. Most derivatives exhibited significant anti-proliferative activities against five cancer cell lines, including MGC-803 and BEL-7402. (Z)-3-(p-Tolyl)-2-(3,4,5-trimethoxyphenyl)acrylonitrile (6h) showed a strong inhibitory effect on MGC-803 cells (IC50 50 50 value of 6h in L-02 cells was 10,000-fold higher than in MGC-803 cells. Compound 6h inhibited proliferation of BEL-7402 cells by arresting at the G2/M phase through up-regulation of cyclin B1 expression, down-regulation of cyclin A and D1 expression, and induction of apoptosis. In addition, 6h inhibited the migration of BEL-7402 cells and the formation of cell colonies.
- Xin, Ya-Bing,Li, Jia-Jun,Zhang, Hong-Jian,Ma, Jun,Liu, Xin,Gong, Guo-Hua,Tian, Yu-Shun
-
p. 1554 - 1564
(2018/10/02)
-
- TYD1608 with selective anti-cancer activity as well as preparation and application thereof
-
The invention provides cyan-containing TYD1608, i.e., (Z)-3-(p-methyl phenyl)-2-(3,4,5-trimethoxyphenyl) acrylonitrile as well as preparation and application thereof, and relates to the field of medicinal compounds with the structure shown in the description. Various anti-cancer medicine in the prior art have the killing capability on cancer cells and also have great toxicity on normal cells; thetreatment of cancer patients is seriously influenced, so that the invention of the medicine with the selective anti-cancer activity on the normal cells is very important. The TYD1608 is synthesized; the compound shows strong proliferation inhibition capability on six kinds of human face cancer cells; in addition, the toxicity on the L-02 normal human liver cells is weak. The IC50 value on the MGC-803 gastric cancer cells is smaller than 0.01 mu M, is better than the clinic common use anti-cancer medicine of taxol; good selective anti-cancer activity is realized. Mechanism study shows that theproliferation inhibition activity of the TYD1608 on BEL-7402 cancer cells is the result of inhibiting the G2/M period in the cell period, inducting early stage and later stage apoptosis, blocking cellmigration, inhibiting cell period relevant protein cyclin A1 and cyclin D1.
- -
-
Paragraph 0012; 0013; 0016-0018
(2018/11/22)
-
- Design and synthesis of 2,6-di(substituted phenyl)thiazolo[3,2-b]-1,2,4-triazoles as α-glucosidase and α-amylase inhibitors, co-relative Pharmacokinetics and 3D QSAR and risk analysis
-
Ten fused heterocyclic derivatives bearing the 2,6-di(subsituted phenyl)thiazolo[3,2-b]-1,2,4-triazoles as central rings were synthesized and structures of the compounds were established by analytical and spectral data using FTIR, EI-MS, 1H NMR and 13C NMR techniques. In vitro inhibitory activities of synthesized compounds on α-amylase, α-glucosidase and α-burylcholinesterase (α-BuChE) were evaluated using a purified enzyme assays. Compound 5c demonstrated strong and selective α-amylase inhibitory activity (IC50?=?1.1?μmol/g). 5?g exhibited excellent inhibition against α-glucosidase (IC50?=?1.2?μmol/g) when compared with acarbose (IC50?=?4.7?μmol/g) as a positive reference. Compound 5i was found to be most potent derivative against α-BuChE with the IC50 of 1.5?μmol/g which was comparable to the value obtained for (4.7?μmol/g) positive control (i.e. galantamine hydrobromide). Molecular dockings of synthesized compounds into the binding sites of human pancreatic α-amylase, intestinal maltase-glucoamylase and neuronal α-butrylcholinesterase allowed to shed light on the affinity and binding mode of these novel inhibitors. Preliminary structure–activity relationship (SAR) studies were carried out to understand the relationship between molecular structural features and inhibition activities of synthesized derivatives. These data suggested that compounds 5c, 5?g and 5i are promising candidates for hitto- lead follow-up in the drug-discovery process for the treatment of Alzheimer's disease and hyperinsulinamia.
- Channar, Pervaiz Ali,Saeed, Aamer,Larik, Fayaz Ali,Rashid, Sajid,Iqbal, Qaiser,Rozi, Maryam,Younis, Saima,Mahar, Jamaluddin
-
p. 499 - 513
(2017/08/08)
-
- Agricultural bactericide derived from gallate, and application
-
The invention provides an agricultural bactericide derived from gallate, and relates to the field of agricultural medicines. The main ingredient of the agricultural bactericide is gallate derivate, wherein the gallate derivate is prepared from a compound with a structure disclosed by a formula (I) and is provided with a hydrophilic functional group-phenolic hydroxyl group. According to the agricultural bactericide prepared from the gallate derivate, various crop harmful bacteria can be inhibited, and the agricultural bactericide especially has a good bacteriostatic effect on apple altermaria leaf spot, botryosphaeria dothidea, rhizoctonia solani, colletotrichum fragariae, potato blight and the like and has good water solubility, and the problem that the gallate derivate prepared in the prior art has poor water solubility is solved.
- -
-
Paragraph 0101; 0102; 0106
(2018/01/11)
-
- Activity of resveratrol triesters against primary acute lymphoblastic leukemia cells
-
Resveratrol is a common polyphenol of plant origin known for its cancer prevention and other properties. Its wider application is limited due to poor water solubility, low stability, and weak bioavailability. To overcome these limitations, a series of 13 novel resveratrol triesters were synthesized previously. In this paper, we describe the synthesis of 3 additional derivatives and the activity of all 16 against primary acute lymphoblastic leukemia cells. Of these, 3 compounds were more potent than resveratrol (IC50?=?10.5?μM) namely: resveratryl triacetate (IC50?=?3.4?μM), resveratryl triisobutyrate (IC50?=?5.1?μM), and resveratryl triisovalerate (IC50?=?4.9?μM); all other derivatives had IC50 values of >10?μM. Further studies indicated that the active compounds caused G1 phase arrest, increased expression of p53, and induced characteristics of apoptotic cell death. Moreover, the compounds were only effective in cycling cells, with cells arrested in G1 phase being refractory.
- Urbaniak, Alicja,Delgado, Magdalena,Kacprzak, Karol,Chambers, Timothy C.
-
supporting information
p. 2766 - 2770
(2017/05/29)
-
- Iron(III)/TEMPO-Catalyzed Synthesis of 2,5-Disubstituted 1,3,4-Oxadiazoles by Oxidative Cyclization under Mild Conditions
-
A simple and efficient cationic Fe(III)/TEMPO-catalyzed oxidative cyclization of aroyl hydrazones has been developed for the synthesis of 2,5-disubstituted 1,3,4-oxadiazole derivatives. The reaction offers a broad scope, good functional-group tolerance, and high yields under mild conditions in the presence of O 2.
- Zhang, Guofu,Yu, Yidong,Zhao, Yiyong,Xie, Xiaoqiang,Ding, Chengrong
-
supporting information
p. 1373 - 1377
(2017/06/27)
-
- 2-BENZYL-INDANONE COMPOUNDS AS ANTICANCER AGENT AND A PROCESS FOR PREPARATION THEREOF
-
The anticancer activity of gallic acid compounds has been invented, in order to obtain new potent and cost effective molecule using in vitro cytotoxicity assay. The invention particularly relates to the gallic acid based new molecules i.e. 2-benzyl indanones represented by structure 1, possessing anticancer activity against human cancer cell lines. The compound also exhibited tubulin polymerisation inhibition. 2-(3',4'-methylenedioxybenzyl)-3-(3",4",5"-trimethoxyphenyl)-indanone- 1 (2), possessing molecular formulae as C29H30O9 was synthesized from gallic acid, exhibits potent in-vivo anticancer activity. Compound 2 was evaluated for acute oral activity in Swiss albino mice and it was found to be well tolerated by the experimental animals up to 300mg/kg body weight. (Formula 1, Formula 2).
- -
-
Page/Page column 10; 13
(2017/02/09)
-
- Gallic acid acylated derivatives having anticancer activity and use thereof
-
The invention discloses gallic acid acylated derivatives having anticancer activity. The gallic acid acylated derivatives have a structural formula shown in the description. The acylated derivatives provided by the invention have good activity to oral cancer cells, have good selectivity and have a good clinical application value.
- -
-
Paragraph 0019; 0020; 0021
(2017/08/28)
-
- Polymer supported Zn-salen complexes: An effective one-pot oxidative esterification of aldehydes to carboxylic esters
-
Polymer-supported Zn-salen (PS-Zn-salen) complexes were synthesized, characterized and used as a catalyst for one-pot oxidative esterification of aldehydes with alcohols. The PS-Zn-salen heterogeneous catalyst exhibited a high-performance for the oxidative esterification of aldehydes to the corresponding methyl/ethyl esters using hydrogen peroxide as a green oxidant. Due to the synergistic effect of polymer support, the heterogeneous catalyst presented superior catalytic activity and afford 100% conversion of 3,4,5-trimethoxybenzaldehyde and 4-chlorobenzaldehyde to corresponding esters under optimized conditions. The different alcohol substrates study (viz. methyl alcohol, ethyl alcohol, allyl alcohol and benzyl alcohol) showed reasonable selectivity for esters, indicating the scope of the catalysts. Significantly, the synthesized complexes possess good hydrophobic/heterogeneous properties, which permit facile reclamation of the catalyst by using mere filtration. Moreover, the effect of counter anions of complex also studied which indicated that there is no appreciable influence on the conversion of product. The catalyst was reused up to 5th successive run with the average conversion of ester 87.4%. Mechanistic studies have recognized that this “one pot” direct oxidative esterification proceeds through acid formation, proven by a GC–MS. The catalyst is also found to be very stable, up to 280?°C, confirmed by the thermo gravimetric study.
- Balinge, Kamlesh Rudreshwar,Khiratkar, Avinash Ganesh,Bhagat, Pundlik Rambhau
-
p. 1085 - 1095
(2017/08/08)
-
- Synthesis method for trimethoprim drug intermediate methyl 3,4,5-trimethoxybenzoate
-
The invention relates to a synthesis method for a trimethoprim drug intermediate methyl 3,4,5-trimethoxybenzoate, which includes the following steps: 0.56mol of stannous chloride, 0.31mol of 3,4,5-hydroxybenzoic acid, 0.36mol to 0.39mol of trimethylamine phosphate and 110ml of sodium chloride solution are added into a reaction vessel with an agitator, a thermometer, a reflux condenser and a dripping funnel, the solution temperature is increased to 40DEG C to 45DEG C, 130ml to 150ml of sodium sulfite solution is added, the agitation speed is controlled at 130rpm to 160rpm, reaction is carried out for 60 to 80 minutes, potassium bisulfite solution is then added to regulate pH to 9 to 10, reaction is carried out for 3 to 4 hours, the solution temperature is decreased to 5DEG C to 9DEG C, and after washing by a saline solution, washing by nitromethane, dehydration by a dehydrating agent and recrystallization in butyl acetate, the methyl 3,4,5-trimethoxybenzoate is obtained. The part by mass of the sodium chloride solution in the steps is 20 to 25 percent, the part by mass of the sodium sulfite solution in the steps is 30 to 35 percent, and the part by mass of the potassium bisulfite solution in the steps is 40 to 45 percent.
- -
-
Paragraph 0007; 0015; 0016
(2016/10/27)
-
- Synthesis and biological evaluation of novel resveratrol-oxadiazole hybrid heterocycles as potential antiproliferative agents
-
A novel class of resveratrol-oxadiazole hybrid compounds was synthesized to screen for their in vitro antiproliferative activity against three human cancer cell lines. All the compounds showed superior antiproliferative activity than the reference compound resveratrol. The most promising active compounds in this series were 1g, 2g, 1c, 2c, 2i and 1a (GI50 0.1 μM), endowed with excellent antiproliferative activity. Thus, we believe that resveratrol-oxadiazole hybrid compounds may possibly be used as a good leads for the development of new antiproliferative agents. Structures of newly synthesized compounds were confirmed by NMR and IR spectral data.
- Murty,Penthala, Raju,Polepalli, Sowjanya,Jain
-
p. 627 - 643
(2016/03/08)
-
- Compound and application thereof
-
The invention discloses a compound and application thereof. The compound is the compound shown in the formula (I) or a stereoisomer or a pharmaceutical acceptable salt or solvate or a prodrug of the compound shown in the formula (I). The compound can restrain tumor cell proliferation through the effect RRM2, and restrain tumor stem cell regeneration, thereby being effectively used for preparing medicine for preventing or treating proliferative diseases and particularly anti-cancer medicine.
- -
-
Paragraph 0771
(2016/10/09)
-
- Novel 1,3,4-oxadiazole/oxime hybrids: Synthesis, docking studies and investigation of anti-inflammatory, ulcerogenic liability and analgesic activities
-
A novel group of 1,3,4-oxadaiazoles, a group known for their anti-inflammatory activity, is hybridized with nitric oxide (NO) releasing group, oxime, for its gastro-protective action and potential synergistic effect. The synthesized hybrids were evaluated for their anti-inflammatory, analgesic, antioxidant and ulcerogenic activities. Most of the tested compounds showed excellent anti-inflammatory activity with compound 8e being more active than indomethacin. They also showed moderate analgesic activity but no antioxidant one. The ability of the synthesized compounds to inhibit COX-1 and COX-2 is studied and the prepared compounds were able to inhibit both COXs non-selectively with IC50s of 0.75–70.50?μM. Docking studies revealed the mode of interaction of the tested compounds into the empty pocket of the isozymes. All of the synthesized compounds interact with COXs active site with energy scores comparable to that of ibuprofen. All compounds showed a safer profile on the stomach tissue integrity compared to conventional NSAIDs. The designed strategy was applied to ibuprofen to introduce ibuprofen/oxadiazole/NO hybrid. The synthesized ibuprofen hybrid is a promising alternative to ibuprofen having similar anti-inflammatory activity but with safer GIT profile.
- Abd-Ellah, Heba S.,Abdel-Aziz, Mohamed,Shoman, Mai E.,Beshr, Eman A.M.,Kaoud, Tamer S.,Ahmed, Al-Shaimaa F.F.
-
supporting information
p. 48 - 63
(2016/09/28)
-
- An efficient nonconventional glycerol-based solid acid catalyzed synthesis and biological evaluation of phosphonate conjugates of 1,2,4-triazole thiones
-
A series of diethyl (3-((5-aryl-1H-1,2,4-triazol-3-yl)thio)propyl)phos-phonates (7a-t) has been synthesized in excellent yields by coupling diethyl (3-bromopropyl)phosphonate and 5-aryl-1H- 1,2,4-triazol-3-thiones employing an efficient, green and nonconventional heterogeneous SO3Hcarbon catalyst derived from glycerol. In addition, a facile and green approach for the esterification of carboxylic acids by utilizing glycerol-based solid acid catalyst has been reported. Structures of the synthesized compounds were characterized by IR, NMR and HRMS studies. These triazole derivatives were screened for their in vitro cytotoxicity using the standard MTT (3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetra-zolium bromide) assay against a panel of five different human cancer cell lines (HeLa: Cervix, A549: Lung, A375: Skin, MDA-MB-231: Breast and T98G: Brain). The antimicrobial activities of the synthesized compounds were investigated against four bacterial strains: Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and three fungal strains: Aspergillus Niger, Aspergillus terreus, Aspergillus fumigatus. Preliminary results indicate that the compound 7f displayed maximum anticancer activity and the compounds 7d, 7e, 7f, 7m and 7q exhibited moderate antibacterial activity. The compounds 7g, 7h, 7o and 7p showed good antifungal activity with high inhibition zone diameter compared to the standard drug.
- Murty, Madugula S.R.,Katiki, Mohana R.,Rao, Busam R.,Narayanan, Sai S.,Anto, Ruby J.,Buddana, Sudhreer K.,Prakasham, Reddy S.,Devi, Bethala L.A.P.,Prasad, Rachapudi B.N.
-
p. 968 - 981
(2016/10/31)
-
- Synthesis and Bioevaluation of 3,6-Diaryl-[1,2,4]triazolo[4,3-b] Pyridazines as Antitubulin Agents
-
A series of 3,6-diaryl-[1,2,4]triazolo[4,3-b]pyridazines were designed as a class of vinylogous CA-4 analogues. The easily isomerized (Z,E)-butadiene linker of vinylogous CA-4 was replaced by a rigid [1,2,4]triazolo[4,3-b]pyridazine scaffold. Twenty-one target compounds were synthesized and exhibited moderate to potent antiproliferative activity. The compound 4q with a 3-amino-4-methoxyphenyl moiety as the B-ring, comparable to CA-4 (IC50 = 0.009-0.012 μM), displayed the highly active antiproliferative activity against SGC-7901, A549, and HT-1080 cell lines with IC50 values of 0.014, 0.008, and 0.012 μM, respectively. Tubulin polymerization experiments indicated that 4q effectively inhibited tubulin polymerization, and immunostaining assay revealed that 4q significantly disrupted tubulin microtubule dynamics. Moreover, cell cycle studies revealed that compound 4q dramatically arrested cell cycle progression at G2/M phase in A549 cells. Molecular modeling studies showed that 4q could bind to the colchicine binding site on microtubules.
- Xu, Qile,Wang, Yueting,Xu, Jingwen,Sun, Maolin,Tian, Haiqiu,Zuo, Daiying,Guan, Qi,Bao, Kai,Wu, Yingliang,Zhang, Weige
-
supporting information
p. 1202 - 1206
(2016/12/18)
-
- Synthesis and antimicrobial activities of various N-phenyl-2-{[5-(3,4,5-trimethoxyphenyl)-1,3,4-oxadiazol-2-yl]sulfanyl}acetamides
-
A new series of various N-phenyl-2-{[5-(3,4,5-trimethoxyphenyl)-1,3,4-oxadiazol-2-yl]sulfanyl}acetamidehave been synthesized by the condensation of 5-(3,4,5-trimethoxyphenyl)-1,3,4-oxadiazole-2-thiol and 2-chloro-N-(aryl)-acetamides. The novel compound structures have been established on the basis of their substituted N-chloro aryl acetamide derivatives. All the compounds have been characterized by FT-IR, mass spectra, 1H and 13C NMR spectroscopy. These new compounds have been evaluated for their in vitro antibacterial and anti-fungal activities.
- Shukla, Maharshi B.,Mahyavanshi, Jyotindra B.,Parmar, Kokila A.
-
p. 374 - 380
(2017/01/18)
-
- Synthesis method for 3,4,5-trimethoxybenzoate
-
The invention discloses a synthesis method for 3,4,5-trimethoxybenzoate. According to the synthesis method, 3,4,5-trimethoxybenzoic acid serves as a raw material, N,N-dimethylformamide serves as solvent, 3,4,5-trimethoxybenzoic acid and N,N-dimethylformamide are subjected to an esterification reaction with chloromethane gas at the temperature of 20 DEG C-60 DEG C, in the reaction process, any one inorganic alkaline compound of potassium carbonate, sodium carbonate, potassium hydroxide and sodium hydroxide serves as an acid binding agent, whether a catalyst is added or not is determined according to the specific reaction condition, and any one or a mixture of polyethylene glycol and sodium bromide serves as the catalyst. The method is simple and practicable, easy and convenient to operate, efficient and environmentally friendly and can be used for commercialized scale production to meet the ever-increasing market requirements.
- -
-
Paragraph 0021
(2016/11/24)
-
- NOVEL SINGLE STEP ESTERIFICATION PROCESS OF ALDEHYDES USING A HETEROGENEOUS CATALYST
-
The present invention relates to a novel simple, efficient and single-step process for esterification of aldehydes using a heterogeneous catalyst with high yields. More particularly, the present invention relates to a novel simple, efficient and single-step process for esterification of aldehydes using Titanium superoxide with greater than 80% yields.
- -
-
Page/Page column 7; 13; 16
(2016/06/20)
-
- Anticancer activity of gallic acid template-based benzylidene indanone derivative as microtubule destabilizer
-
Benzylidene indanones have been designed and synthesized from gallic acid, a plant phenolic acid as possible anticancer agent. The best analogue of the series, that is, 3-(3′,4′,5′-trimethoxyphenyl)-4,5,6-trimethoxy-2-(4?-nitrobenzylidene)-indan-1-one (8) exhibited potent cytotoxicity (IC50=3–10?μm) against several human cancer cell lines through microtubule destabilization (IC50=1.54?μm) after occupying colchicine-binding site of β-tubulin. In cell cycle analysis, compound 8 exerted G2/M phase arrest in both MCF-7 and MDA-MB-231 cells and induced apoptosis. It reduced 34.8% solid tumor in in vivo Ehrlich ascite carcinoma in Swiss albino mice at 30?mg/kg dose. In acute oral toxicity experiment, it was tolerable up to 300?mg/kg doses in Swiss albino mice. The lead compound 8 needs to be optimized for better activity.
- Singh, Aastha,Fatima, Kaneez,Srivastava, Ankita,Khwaja, Sadiya,Priya, Dev,Singh, Arjun,Mahajan, Girish,Alam, Sarfaraz,Saxena, Ajit K.,Mondhe,Luqman, Suaib,Chanda, Debabrata,Khan, Feroz,Negi, Arvind S.
-
p. 625 - 634
(2016/10/25)
-
- Method for synthesizing methyl 3,4,5-trimethoxybenzoate by using one-step method
-
The invention provides a method for synthesizing methyl 3,4,5-trimethoxybenzoate by using a one-step method. The method comprises the following steps: by taking gallic acid as a raw material, performing esterification reaction on N,N-dimethyl formamide as a solvent and a chloromethane gas, thereby preparing methyl 3,4,5-trimethoxybenzoate at one step. In the reaction process, potassium carbonate is taken as an acid-binding agent. The method is convenient and feasible, simple and convenient to operate, efficient and environmentally friendly, and applicable to commercial large-scale production, and ever-increasing market requirements can be met.
- -
-
Paragraph 0020; 0021
(2016/11/02)
-
- Design and synthesis of a series of serine derivatives as small molecule inhibitors of the SARS coronavirus 3CL protease
-
Synthesis of serine derivatives having the essential functional groups for the inhibitor of SARS 3CL protease and evaluation of their inhibitory activities using SARS 3CL R188I mutant protease are described. The lead compounds, functionalized serine derivatives, were designed based on the tetrapeptide aldehyde and Bai's cinnamoly inhibitor, and additionally performed with simulation on GOLD softwear. Structure activity relationship studies of the candidate compounds were given reasonable inhibitors ent-3 and ent-7k against SARS 3CL R188I mutant protease. These inhibitors showed protease selectivity and no cytotoxicity.
- Konno, Hiroyuki,Wakabayashi, Masaki,Takanuma, Daiki,Saito, Yota,Akaji, Kenichi
-
supporting information
p. 1241 - 1254
(2016/03/01)
-
- N-(1'-naphthyl)-3,4,5-trimethoxybenzohydrazide as microtubule destabilizer: Synthesis, cytotoxicity, inhibition of cell migration and in vivo activity against acute lymphoblastic leukemia
-
Tubulin-interacting agents, like vinca alkaloid and taxanes, play a fundamental role in cancer chemotherapy, making cellular microtubules (MT), one of the few validated anticancer targets. Cancer resistance to classical MT inhibitors has motivated the development of novel molecules with increased efficacy and lower toxicity. Aiming at designing structurally-simple inhibitors of MT assembly, we synthesized a series of thirty-one 3,4,5-trimethoxy-hydrazones and twenty-five derivatives or analogs. Docking simulations suggested that a representative N-acylhydrazone could adopt an appropriate stereochemistry inside the colchicine-binding domain of tubulin. Several of these compounds showed anti-leukemia effects in the nanomolar concentration range. Interference with MT polymerization was validated by the compounds' ability to inhibit MT assembly at the biochemical and cellular level. Selective toxicity investigations done with the most potent compound, a 3,4,5-trimethoxy-hydrazone with a 1-naphthyl group, showed remarkably selective toxicity against leukemia cells in comparison with stimulated normal lymphocytes, and no acute toxicity in vivo. Finally, this molecule was as active as vincristine in a murine model of human acute lymphoblastic leukemia at a weekly dose of 1 mg/kg.
- Salum, Lívia B.,Mascarello, Alessandra,Canevarolo, Rafael R.,Altei, Wanessa F.,Laranjeira, Angelo B.A.,Neuenfeldt, Patrícia D.,Stumpf, Taisa R.,Chiaradia-Delatorre, Louise D.,Vollmer, Laura L.,Daghestani, Hikmat N.,De Souza Melo, Carolina P.,Silveira, André B.,Leal, Paulo C.,Frederico, Marisa J.S.,Do Nascimento, Leandro F.,Santos, Adair R.S.,Andricopulo, Adriano D.,Day, Billy W.,Yunes, Rosendo A.,Vogt, Andreas,Yunes, José A.,Nunes, Ricardo J.
-
p. 504 - 518
(2015/05/13)
-
- A Strained Disilane-Promoted Carboxylation of Organic Halides with CO2 under Transition-Metal-Free Conditions
-
By using a strained four-membered ring disilane (3,4-benzo-1,1,2,2-tetraethyldisilacyclobutene) and CsF, a wide range of aryl, alkenyl, alkynyl, benzyl, allyl, and alkyl halides was successfully carboxylated under an ambient CO2 atmosphere (CO2 balloon) at room temperature within 2 h. In this carboxylation, a highly reactive silyl anion, which is generated from the disilane and CsF, is a key to facilitating the formation of a carbanion equivalent. The resulting anionic species can be trapped with CO2 to produce carboxylic acids with high efficiency.
- Mita, Tsuyoshi,Suga, Kenta,Sato, Kaori,Sato, Yoshihiro
-
supporting information
p. 5276 - 5279
(2015/11/18)
-
- Direct oxidative esterification of alcohols and hydration of nitriles catalyzed by a reusable silver nanoparticle grafted onto mesoporous polymelamine formaldehyde (AgNPs@mPMF)
-
A nitrogen-rich mesoporous organic polymer was synthesized as a novel support. A silver nanoparticle was synthesized and grafted onto it. The prepared catalyst (AgNPs@mPMF) was characterized by powder X-ray diffraction (XRD), scanning electron microscopy(SEM) and energy dispersive X-ray spectrometry (EDS), thermogravimetric analysis (TGA), high-resolution transmission electron microscopy (HRTEM), UV-vis diffuse reflectance spectroscopy (DRS), N2 adsorption, Raman spectroscopy and EPR study. The catalytic activity was evaluated for the oxidative esterification reaction of alcohols and hydration of nitriles. The oxidative esterification reaction was carried out for various activated alcohols giving excellent yields of the corresponding ester products. The catalyst was also efficient in the hydration of nitriles. Both reactions were optimized by varying the bases, temperatures and solvents. The catalyst can be facilely recovered and reused six times without a significant decrease in its activity and selectivity.
- Ghosh, Kajari,Iqubal, Md. Asif,Molla, Rostam Ali,Mishra, Ashutosh,Kamaluddin,Islam, Sk Manirul
-
p. 1606 - 1622
(2015/04/27)
-
- N-Heterocyclic Carbene-Mediated Oxidative Electrosynthesis of Esters in a Microflow Cell
-
An efficient N-heterocyclic carbene (NHC)-mediated oxidative esterification of aldehydes has been achieved in an undivided microfluidic electrolysis cell at ambient temperature. Productivities of up to 4.3 g h-1 in a single pass are demonstrated, with excellent yields and conversions for 19 examples presented. Notably, the oxidative acylation reactions were shown to proceed with a 1:1 stoichiometry of aldehyde and alcohol (for primary alcohols), with remarkably short residence times in the electrolysis cell (13 s), and without added electrolyte. (Chemical Equation Presented).
- Green, Robert A.,Pletcher, Derek,Leach, Stuart G.,Brown, Richard C. D.
-
supporting information
p. 3290 - 3293
(2015/07/15)
-
- An efficient one-pot oxidative esterification of aldehydes to carboxylic esters using B(C6F5)3-TBHP
-
A simple and efficient protocol for oxidative esterification of diverse aldehydes with alcohols was accomplished with tert-butyl hydroperoxide and 1 mol % of tris(pentafluorophenyl)borane [B(C6F5)3] to generate the corresponding esters in good to excellent yields. The present protocol represents compatibility with wide range of functional groups as well as exceptional tolerance toward acid labile protecting groups such as TBDPS, TBDMS, acetonide, and Boc.
- Guggilapu, Sravanthi Devi,Prajapti, Santosh Kumar,Babu, Bathini Nagendra
-
supporting information
p. 889 - 892
(2015/02/05)
-
- Titanium superoxide-a stable recyclable heterogeneous catalyst for oxidative esterification of aldehydes with alkylarenes or alcohols using TBHP as an oxidant
-
Titanium superoxide efficiently catalysed the oxidative esterification of aldehydes with alkylarenes or alcohols, under truly heterogeneous conditions, to afford the corresponding benzyl and alkyl esters in excellent yields. Mechanistic studies have established that this "one pot" direct oxidative esterification process proceeds through a radical pathway, proven by a FTIR spectral study of a titanium superoxide-aldehyde complex as well as spin trapping experiments with TEMPO. The intramolecular version of this protocol has been successfully demonstrated in the concise synthesis of 3-butylphthalide, an anti-convulsant drug.
- Dey, Soumen,Gadakh, Sunita K.,Sudalai
-
p. 10631 - 10640
(2015/11/17)
-
- N-2-Hydroxybenzaldehyde acylhydrazone-Fe(iii) complex: Synthesis, crystal structure and its efficient and selective N-methylation
-
N-Methyl-N′-2-hydroxybenzaldehyde acylhydrazones have been chemospecifically synthesized in good yield by N-methylation of the Fe(iii) complexes of N-2-hydroxybenzaldehyde acylhydrazones with methyl iodide in tetrahydrofuran. The reaction proceeds with the exclusive formation of the N-methyl derivative without any concurrent O-methylation side reactions. In addition, the N-methylation reaction occurred simultaneously with a complete deprotection step (elimination of the metal ion). As a result, the N-methyl product was obtained in excellent purity without time-consuming chromatographic workup. A free N-2-hydroxybenzaldehyde acylhydrazone ligand could not be methylated under the same conditions. This journal is the Partner Organisations 2014.
- Li, Zhiyou,Wu, Lamei,Zhang, Tao,Huang, Zhengxi,Qiu, Guofu,Zhou, Zhongqiang,Jin, Longfei
-
p. 7554 - 7560
(2014/05/20)
-
- ACYL-HYDRAZONE AND OXADIAZOLE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME AND USES THEREOF
-
The present invention relates to acyl-hydrazone compounds, in particular 3,4,5-trimethoxyphenyl-hydrazide derivatives, as well as the oxadiazole analogs thereof and other similar compounds, and to the pharmaceutical use of the same for the treatment of various diseases associated with cell proliferation, such as leukemias, including acute lymphoblastic leukemia (ALL), tumours and inflammation. Acyl-hydrazones have been obtained having activity similar to that of the compound used as a standard in experiments (colchicine). The greater selectivity of the compounds according to the invention is an important feature, associated with fewer side effects than the pharmaceuticals used at present in clinical treatments. The synthetised acyl-hydrazones, more particularly the compounds 02 and 07, exhibited important anti-leukemic activity, which suggests 02 and 07 as candidates to pharmaceutical prototypes, or to pharmaceuticals for the treatment of leukemias, in particular acute lymphoblastic leukemia (ALL), tumours and other proliferative diseases, such as inflammation. The action mechanism of the most active compounds was determined by using DNA microarrays and subsequent tests indicated by the chip, besides selectivity studies in healthy human lymphocytes.
- -
-
Paragraph 0069
(2014/10/15)
-