- Photoconversion of β-Lapachone to α-Lapachone via a Protonation-Assisted Singlet Excited State Pathway in Aqueous Solution: A Time-Resolved Spectroscopic Study
-
The photophysical and photochemical reactions of β-lapachone were studied using femtosecond transient absorption, nanosecond transient absorption, and nanosecond time-resolved resonance Raman spectroscopy techniques and density functional theory calculations. In acetonitrile, β-lapachone underwent an efficient intersystem crossing to form the triplet state of β-lapachone. However, in water-rich solutions, the singlet state of β-lapachone was predominantly quenched by the photoinduced protonation of the carbonyl group at the β position (O9). After protonation, a series of fast reaction steps occurred to eventually generate the triplet state α-lapachone intermediate. This triplet state of α-lapachone then underwent intersystem crossing to produce the ground singlet state of α-lapachone as the final product. 1,2-Naphthoquinone is examined in acetonitrile and water solutions in order to elucidate the important roles that water and the pyran ring play during the photoconversion from β-lapachone to α-lapachone. β-Lapachone can also be converted to α-lapachone in the ground state when a strong acid is added to an aqueous solution. Our investigation indicates that β-lapachone can be converted to α-lapachone by photoconversion in aqueous solutions by a protonation-assisted singlet excited state reaction or by an acid-assisted ground state reaction.
- Du, Lili,Li, Ming-De,Zhang, Yanfeng,Xue, Jiadan,Zhang, Xiting,Zhu, Ruixue,Cheng, Shun Cheung,Li, Xuechen,Phillips, David Lee
-
-
Read Online
- 1,2,3-Triazole-, arylamino- and thio-substituted 1,4-naphthoquinones: Potent antitumor activity, electrochemical aspects, and bioisosteric replacement of C-ring-modified lapachones
-
1,2,3-Triazole-, arylamino- and thio-substituted naphthoquinones (24, 8, and 2 representatives, respectively) were synthesized in moderate yields and evaluated against several human cancer cell lines (blood, ovarian, breast, central nervous system, colon, and prostate cancers and melanoma), showing, for some of them, IC50 values below 2 μM. The cytotoxic potential of the tested naphthoquinones was also assayed on non-tumor cells such as human peripheral blood mononucluear cells (PBMC) and two murine fibroblast lines (L929 and V79 cells). α-Lapachone- and nor-α-lapachone-based 1,2,3-triazoles and arylamino-substituted naphthoquinones showed potent cytotoxicity against different cancer cell lines. The compounds may represent promising new lead derivatives for anticancer drug development. The electrochemical properties of selected compounds were evaluated in an attempt to correlate them with antitumor activity.
- Da Cruz, Eduardo H.G.,Hussene, Caio M.B.,Dias, Gleiston G.,Diogo, Emilay B.T.,De Melo, Isadora M.M.,Rodrigues, Bernardo L.,Da Silva, Mauro G.,Valen?a, Wagner O.,Camara, Celso A.,De Oliveira, Ronaldo N.,De Paiva, Yen G.,Goulart, Marilia O.F.,Cavalcanti, Bruno C.,Pessoa, Claudia,Da Silva Júnior, Eufranio N.
-
-
Read Online
- Naphthoquinone-based hydrazone hybrids: Synthesis and potent activity against cancer cell lines
-
Background: Natural naphthoquinones have shown diversified biological activities including antibacterial, antifungal, antimalarial, and cytotoxic activities. However, they are also compounds with acute cytotoxicity, immunotoxicity, carcinogenesis, and cardio-and hepatotoxicity, and the modification at their redox center is an interesting strategy to overcome such harmful activity. Objective: In this study, four novel semisynthetic hydrazones, derived from the isomers α-and βlapachones (α and β, respectively) and coupled with the drugs hydralazine (HDZ) and isoniazid (ACIL), were prepared, evaluated by electrochemical methods and assayed for anticancer activity. Methods: The semisynthetic hydrazones were obtained and had their molecular structures established by NMR, IR, and MS. Anticancer activity was evaluated by cell viability determined by reduction of 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide (MTT). The electrochemical studies, mainly cyclic voltammetry, were performed, in aprotic and protic media. Results: The study showed that the compounds 2, 3, and 4 were active against at least one of the cancer cell lines evaluated, compounds 3 and 4 being the most cytotoxic. Toward HL-60 cells, compound 3 was 20x more active than β-lapachone, and 3x more cytotoxic than doxorubicin. Furthermore, 3 showed an SI value of 39.62 for HL-60 cells. Compound 4 was active against all cancer cells tested, with IC50 values in the range 2.90–12.40 μM. Electrochemical studies revealed a profile typical of self-protonation and reductive cleavage, dependent on the supporting electrolyte. Conclusion: These results therefore indicate that compounds 3 and 4 are strong candidates as prototypes of new antineoplastic drugs.
- Gonsalves, Arlan de Assis,Pessoa, Claudia,Silva, Maria Francilene Souza,Silva, Thaissa Lucio,Araújo, Cle?nia Roberta Melo,Araújo, Edigênia Cavalcante,Goulart, Marília Oliveira Fonseca,Guimar?es, Délis Galv?o,Rolim, Larissa Araújo,Santos, Danyelle Candido,Santos, Victória Laysna Dos Anjos,da Costa, Marcília Pinheiro,de Oliveira, Fátima de Cássia Evangelista
-
p. 945 - 955
(2021/11/30)
-
- Ligand-based design, synthesis and biochemical evaluation of potent and selective inhibitors of Schistosoma mansoni dihydroorotate dehydrogenase
-
Schistosomiasis ranks second only to malaria as the most common parasitic disease worldwide. 700 million people are at risk and 240 million are already infected. Praziquantel is the anthelmintic of choice but decreasing efficacy has already been documented. In this work, we exploited the inhibition of Schistosoma mansoni dihydroorotate dehydrogenase (SmDHODH) as a strategy to develop new therapeutics to fight schistosomiasis. A series of quinones (atovaquone derivatives and precursors) was evaluated regarding potency and selectivity against both SmDHODH and human DHODH. The best compound identified is 17 (2-hydroxy-3-isopentylnaphthalene-1,4-dione) with IC50 = 23 ± 4 nM and selectivity index of 30.83. Some of the new compounds are useful pharmacological tools and represent new lead structures for further optimization.
- Calil, Felipe A.,David, Juliana S.,Chiappetta, Estela R.C.,Fumagalli, Fernando,Mello, Rodrigo B.,Leite, Franco H.A.,Castilho, Marcelo S.,Emery, Flavio S.,Nonato, M.Cristina
-
p. 357 - 366
(2019/02/19)
-
- Design of hybrid molecules as antimycobacterial compounds: Synthesis of isoniazid-naphthoquinone derivatives and their activity against susceptible and resistant strains of Mycobacterium tuberculosis
-
Isoniazid-naphthoquinone hybrids were synthesized and evaluated against a susceptible (H37Rv) strain and two isoniazid-resistant strains (INHR1 and INHR2) of Mycobacterium tuberculosis. The antimycobacterial activity of the derivatives was determined based on the resazurin microtiter assay and their cytotoxicity in adhered mouse monocyte macrophage J774.A1 cells (ATCC TIB-67). Of the twenty-two compounds evaluated against the three strains of M. tuberculosis, twenty-one presented some activity against the H37Rv and INHR1 (katG S315T) or INHR2 (inhA C(?5)T) strains. Compounds 1a, 2a, and 8a were effective against the INHR1 strain, and compounds 1a, 1b, 2a, 3a, 5a, 5b and 8a were effective against the INHR2 strain, with MICs in the range of 3.12–6.25 μg/mL. Compounds 1b and 5b were the most active against H37Rv, with MIC of 0.78 μg/mL. Based on the selectivity index, 1b and 5b can be considered safe as a drug candidate compounds. These results demonstrate that quinoidal compounds can be used as promising scaffolds for the development of new anti-TB drugs and hybrids with activity against M. tuberculosis-susceptible and INH-resistant strains.
- Reis, Wallace J.,Bozzi, ícaro A.O.,Ribeiro, Matheus F.,Halicki, Priscila C.B.,Ferreira, Laís A.,Almeida da Silva, Pedro E.,Ramos, Daniela F.,de Simone, Carlos A.,da Silva Júnior, Eufranio N.
-
p. 4143 - 4150
(2019/08/06)
-
- α- and β-Lapachone Isomerization in Acidic Media: Insights from Experimental and Implicit/Explicit Solvation Approaches
-
Combined experimental and mixed implicit/explicit solvation approaches were employed to gain insights into the origin of switchable regioselectivity of acid-catalyzed lapachol cyclization and α-/β-lapachone isomerization. It was found that solvating species under distinct experimental conditions stabilized α- and β-lapachone differently, thus altering the identity of the thermodynamic product. The energy profile for lapachol cyclization revealed that this process can occur with low free-energy barriers (lower than 8.0 kcal mol?1). For α/β isomerization in a dilute medium, the computed enthalpic barriers are 15.1 kcal mol?1 (α→β) and 14.2 kcal mol?1 (β→α). These barriers are lowered in concentrated medium to 11.5 and 12.6 kcal mol?1, respectively. Experimental determination of isomers ratio was quantified by HPLC and NMR measurements. These findings provide insights into the chemical behavior of lapachol and lapachone derivatives in more complex environments.
- Delarmelina, Maicon,Nicoletti, Caroline D.,de Moraes, Marcela C.,Futuro, Debora O.,Bühl, Michael,de C. da Silva, Fernando,Ferreira, Vitor F.,de M. Carneiro, José W.
-
-
- Ruthenium-catalyzed C-H oxygenation of quinones by weak O-coordination for potent trypanocidal agents
-
Ruthenium-catalysis enabled the C-5 selective C-H oxygenation of naphthoquinones, and also sets the stage for the site-selective introduction of a hydroxyl group into anthraquinones. A-ring modified naphthoquinoidal compounds represent an important class of bioactive quinones for which the present study encompasses the first C-H oxygenation strategy by weak O-coordination.
- Dias, Gleiston G.,Rogge, Torben,Kuniyil, Rositha,Jacob, Claus,Menna-Barreto, Rubem F. S.,Da Silva Júnior, Eufranio N.,Ackermann, Lutz
-
supporting information
p. 12840 - 12843
(2018/11/30)
-
- Discovery of quinone-directed antitumor agents selectively bioactivated by NQO1 over CPR with improved safety profile
-
In this work, we mainly focused on discovering compounds with good selectivity for NQO1 over CPR. The NQO1-mediated two-electron reduction of compounds would kill cancer cells selectively, while CPR-mediated one-electron reduction would induce potential hepatotoxicity. Several novel quinone-directed antitumor agents were discovered as specific NQO1 substrates through structure-activity relationship studies. Among them, compound 3,7,8-trimethylnaphtho[1,2-b]furan-4,5-dione (12b) emerged as the most specific substrate of the two-electron oxidoreductase NQO1 and could hardly be reduced by CPR. It afforded the highest selectivity between NQO1/CPR (selectivity ratio = 6.37), much higher than the control β-lapachone (selectivity ratio = 1.36), indicated 12b may possess superior safety profile. The electrochemical studies provided a reasonable explanation to the good selectivity toward NQO1. Molecular docking studies supported that 12b was capable of forming additional C-H … π interactions with Trp105 and Phe178 residues compared to the control β-lap. In addition, compound 12b was shown to kill cancer cells efficiently both in vitro and in vivo model. This work gave us a promising and novel scaffold for further investigation.
- Bian, Jinlei,Li, Xiang,Wang, Nan,Wu, Xingsen,You, Qidong,Zhang, Xiaojin
-
-
- LAPACHONE DERIVATIVES CONTAINING TWO REDOX CENTERS AND METHODS OF USE THEREOF
-
Provided herein are compounds containing two redox centers including a chalcogen redox center of the formula: wherein: R1, R2, X1, X2, Y1, and m are as defined herein. Also provided herein are pharmaceutical composition of the present compounds and methods of treatment using the compounds including their use in the treatment of cancer.
- -
-
Paragraph 00122
(2017/05/10)
-
- Synthesis and antitumor activity of selenium-containing quinone-based triazoles possessing two redox centres, and their mechanistic insights
-
Selenium-containing quinone-based 1,2,3-triazoles were synthesized using click chemistry, the copper catalyzed azide-alkyne 1,3-dipolar cycloaddition, and evaluated against six types of cancer cell lines: HL-60 (human promyelocytic leukemia cells), HCT-11
- Da Cruz, Eduardo H.G.,Silvers, Molly A.,Jardim, Guilherme A.M.,Resende, Jarbas M.,Cavalcanti, Bruno C.,Bomfim, Igor S.,Pessoa, Claudia,De Simone, Carlos A.,Botteselle, Giancarlo V.,Braga, Antonio L.,Nair, Divya K.,Namboothiri, Irishi N.N.,Boothman, David A.,Da Silva Júnior, Eufranio N.
-
-
- Synthesis, Characterization, and Antileukemic Properties of Naphthoquinone Derivatives of Lawsone
-
Naphthoquinones are considered privileged structures for anticancer drug molecules. The Heck reaction of 2-hydroxy-1,4-naphthoquinone (lawsone) with 1-bromo-3-methyl-2-butene offered easy access to lapachol. Several naturally occurring linear and angular heterocyclic quinoids (α-lapachone, β-lapachone, dunnione, and related analogues) were prepared from lapachol. Furthermore, we demonstrated that the synthetic naphthoquinones inhibit cell proliferation in human leukemia HL-60 cells. In particular, angular-type derivatives were found to possess moderate cytotoxicity and to elevate the levels of intracellular glutathione disulfide (GSSG). Our work highlights the significant potential of naturally occurring angular-series naphthoquinones as antileukemic agents.
- Inagaki, Ryuta,Ninomiya, Masayuki,Tanaka, Kaori,Koketsu, Mamoru
-
p. 1413 - 1423
(2015/08/03)
-
- Naphthoquinone-based chalcone hybrids and derivatives: Synthesis and potent activity against cancer cell lines
-
Novel naphthoquinone-based chalcones were prepared from the reaction between 3-bromo-nor-β-lapachone and amino-chalcones. Lapachone derivatives are also described here. All the substances were evaluated against cancer and normal cell lines and several compounds demonstrated potent antitumor activity. This journal is
- Jardim, Guilherme A. M.,Guimares, Tiago T.,Pinto, Maria Do Carmo F.R.,Cavalcanti, Bruno C.,De Farias, Kaio M.,Pessoa, Claudia,Gatto, Claudia C.,Nair, Divya K.,Namboothiri, Irishi N. N.,Da Silva Jnior, Eufrnio N.
-
p. 120 - 150
(2015/02/02)
-
- On the investigation of hybrid quinones: Synthesis, electrochemical studies and evaluation of trypanocidal activity
-
In our continued search for novel trypanocidal compounds, arylamine, chalcone, triazolic, triazole-carbohydrate and chalcogenium derivatives containing a naphthoquinone scaffold were prepared; in addition to electrochemical studies, these compounds were evaluated against the infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease. Among the thirty-eight compounds herein evaluated, six were found to be more potent against trypomastigotes than the standard drug benznidazole, with IC50/24 h values between 52.9 and 89.5 μM.
- Jardim, Guilherme A. M.,Reis, Wallace J.,Ribeiro, Matheus F.,Ottoni, Flaviano M.,Alves, Ricardo J.,Silva, Thaissa L.,Goulart, Marilia O. F.,Braga, Antonio L.,Menna-Barreto, Rubem F. S.,Salom?o, Kelly,De Castro, Solange L.,Da Silva Júnior, Eufranio N.
-
p. 78047 - 78060
(2015/09/28)
-
- Lewis acid mediated highly regioselective intramolecular cyclization for the synthesis of β-lapachone
-
A highly regioselective intramolecular cyclization of lapachol mediated by Lewis acids including NbCl5, AlCl3, and FeCl3 was developed for synthesizing β-lapachone in excellent yields without any formation of the isomer α-lapachone. This procedure was efficient, mild, and easily scalable that avoided using highly hazardous concd H 2SO4. In the case of ZrCl4 the cyclization was found to give α-lapachone as the main product. A possible mechanism for the Lewis acid mediated cyclization was also discussed.
- Bian, Jinlei,Deng, Bang,Zhang, Xiaojin,Hu, Tianhan,Wang, Nan,Wang, Wei,Pei, Haixiang,Xu, Yu,Chu, Hongxi,Li, Xiang,Sun, Haopeng,You, Qidong
-
p. 1475 - 1478
(2014/03/21)
-
- Electronic structure and gas-phase chemistry of protonated α- And β-quinonoid compounds: A mass spectrometry and computational study
-
Rationale: The use of quinonoid compounds against tropical diseases and as antitumor agents has prompted the search for new naturally occurring and synthetic derivatives. Among these quinonoid compounds, lapachol and its isomers (α- and β-lapachone) serve as models for the synthesis of new compounds with biological activity, and the use of electrospray ionization tandem mass spectrometry (ESI-MS/MS) analysis as a tool to elucidate and characterize these products has furnished important information about these compounds. Methods: ESI-MS/MS analysis under collision-induced dissociation conditions was used to describe the fragmentation mechanisms for protonated 1,4-naphthoquinone, 1,2-naphthoquinone, α-lapachone, and β-lapachone. The B3LYP/6-31+G(d,p) model was used to obtain proton affinities, gas-phase basicities, and molecular electrostatic potential maps, thus indicating the probable protonation sites. Fragmentation pathways were suggested on the basis of the relative enthalpies of the product ions. Results: The ESI-MS signals of the cationized molecules of ortho quinonoid compounds were more intense than those of the protonated molecule. Formation of the major product ions with m/z 187 from protonated α- and β-lapachone has been attributed to a retro-Diels-Alder (RDA) reaction. Conclusions: MS/MS studies on lapachol isomers (α- and β-lapachone) will facilitate the interpretation of the liquid chromatography (LC)-MS/MS analysis of new metabolites. MS/MS data on the 1,4-naphthoquinone, 1,2-naphthoquinone, α-lapachone and β-lapachone core will help characterize new derivatives from in vitro/in vivo metabolism studies in complex matrices. The product ions revealed the major fragmentation mechanisms and these ions will serve as diagnostic ions to identify each studied compound. Copyright
- Vessecchi, Ricardo,Emery, Flávio S.,Lopes, Norberto P.,Galembeck, Sérgio E.
-
p. 816 - 824
(2013/05/08)
-
- Cytotoxicity of lapachol, β-lapachone and related synthetic 1,4-naphthoquinones against oesophageal cancer cells
-
Naphthoquinones have been found to have a wide range of biological activities, including cytotoxicity to cancer cells. The secondary metabolites lapachol, α- and β-lapachone and a series of 25 related synthetic 1,4-naphthoquinones were screened against the oesophageal cancer cell line (WHCO1). Most of the compounds exhibited enhanced cytotoxicity (IC50 1.6-11.7 μM) compared to the current drug of choice cisplatin (IC 50 = 16.5 μM). This study also established that the two new synthetic halogenated compounds 12a and 16a (IC50 = 3.0 and 7.3 μM) and the previously reported compound 11a (IC50 = 3.9 μM), were non-toxic to NIH3T3 normal fibroblast cells. Cell death of oesophageal cancer cells by processes involving PARP cleavage caused by 11a was shown to be associated with elevated c-Jun levels, suggesting a role for this pathway in the mechanism of action of this cohort of naphthoquinone compounds.
- Sunassee, Suthananda N.,Veale, Clinton G.L.,Shunmoogam-Gounden, Nelusha,Osoniyi, Omalaja,Hendricks, Denver T.,Caira, Mino R.,De La Mare, Jo-Anne,Edkins, Adrienne L.,Pinto, Antonio V.,Da Silva Junior, Eufranio N.,Davies-Coleman, Michael T.
-
-
- Potent naphthoquinones against antimony-sensitive and -resistant Leishmania parasites: Synthesis of novel α- And nor-α-lapachone-based 1,2,3-triazoles by copper-catalyzed azide-alkyne cycloaddition
-
Continuing our screening program for novel anti-parasite compounds, we synthesized seven 1,4-naphthoquinones coupled to 1,2,3-triazoles, five nor-β-lapachone-based 1,2,3-triazoles and ten α-lapachone-based 1,2,3-triazoles. These and other naphthoquinonoid
- Guimar?es, Tiago T.,Pinto, Maria Do Carmo F.R.,Lanza, Juliane S.,Melo, Maria N.,Do Monte-Neto, Rubens L.,De Melo, Isadora M.M.,Diogo, Emilay B.T.,Ferreira, Vitor F.,Camara, Celso A.,Valen?a, Wagner O.,De Oliveira, Ronaldo N.,Frézard, Frédéric,Da Silva Júnior, Eufranio N.
-
p. 523 - 530
(2013/07/27)
-
- Synthesis and anti-Trypanosoma cruzi activity of naphthoquinone-containing triazoles: Electrochemical studies on the effects of the quinoidal moiety
-
In our continued search for novel trypanocidal compounds, twenty-six derivatives of para- and ortho-naphthoquinones coupled to 1,2,3-triazoles were synthesized. These compounds were evaluated against the infective bloodstream form of Trypanosoma cruzi, th
- Diogo, Emilay B.T.,Dias, Gleiston G.,Rodrigues, Bernardo L.,Guimaraes, Tiago T.,Valenca, Wagner O.,Camara, Celso A.,De Oliveira, Ronaldo N.,Da Silva, Mauro G.,Ferreira, Vitor F.,De Paiva, Yen Galdino,Goulart, Marilia O.F.,Menna-Barreto, Rubem F.S.,De Castro, Solange L.,Da Silva Junior, Eufranio N.
-
p. 6337 - 6348
(2013/10/22)
-
- Biomimetic in vitro oxidation of lapachol: A model to predict and analyse the in vivo phase i metabolism of bioactive compounds
-
The bioactive naphtoquinone lapachol was studied in vitro by a biomimetic model with Jacobsen catalyst (manganese(III) salen) and iodosylbenzene as oxidizing agent. Eleven oxidation derivatives were thus identified and two competitive oxidation pathways postulated. Similar to Mn(III) porphyrins, Jacobsen catalyst mainly induced the formation of para-naphtoquinone derivatives of lapachol, but also of two ortho-derivatives. The oxidation products were used to develop a GC-MS (SIM mode) method for the identification of potential phase I metabolites in vivo. Plasma analysis of Wistar rats orally administered with lapachol revealed two metabolites, α-lapachone and dehydro-α-lapachone. Hence, the biomimetic model with a manganese salen complex has evidenced its use as a valuable tool to predict and elucidate the in vivo phase I metabolism of lapachol and possibly also of other bioactive natural compounds.
- Niehues, Michael,Barros, Valeria Priscila,Emery, Flavio Da Silva,Dias-Baruffi, Marcelo,Assis, Marilda Das Dores,Lopes, Norberto Peporine
-
experimental part
p. 804 - 812
(2012/09/10)
-
- β-Lapachone analogs with enhanced antiproliferative activity
-
In this study, we describe the synthesis of a series of α- and β-lapachone containing hydroxyl or methoxyl groups on the benzene ring, by means of the selective acid promoted cyclization of the appropriate lapachol analog. The evaluation of the antiproliferative activity in human solid tumor cell lines provided 7-hydroxy-β-lapachone as lead with enhanced activity over the parent drug β-lapachone. Cell cycle studies, protein expression experiments, and reactive oxygen species analysis revealed that, similarly to β-lapachone, ROS formation and DNA damage are critical factors in the cellular toxicity of 7-hydroxy-β-lapachone.
- Rios-Luci, Carla,Bonifazi, Evelyn L.,Leon, Leticia G.,Montero, Juan C.,Burton, Gerardo,Pandiella, Atanasio,Misico, Rosana I.,Padron, Jose M.
-
experimental part
p. 264 - 274
(2012/08/28)
-
- Concise synthesis of (±)-rhinacanthin A, dehydro α-lapachone, and β-lapachone, and pyranonaphthoquinone derivatives
-
A concise synthesis of (±)-rhinacanthin A is achieved in two steps by epoxidation of dehydro-α-lapachone, followed by chemo-and regioselective reduction. Dehydro-α-lapachone was also synthesized in two steps starting from 4-methoxy-1-naphthol by ethylenediamine diaetate (EDDA)-catalyzed benzopyran formation and a CAN-mediated oxidation reaction. β-Lapachone was synthesized in three steps from 4-methoxy-1-naphthol by benzopyran formation, catalytic hydrogenation, and Jones oxidation. As additional reactions, synthesis of pyranonaphthoquinone derivatives with the pyranokunthone B skeleton has been achieved in a single step from readily available 2-hydroxy-6-methoxy-1,4-naphthoquinone and 2-hydroxy-7-methoxy-1,4- naphthoquinone.
- Wang, Xue,Chen, Ye,Lee, Yong Rok
-
p. 153 - 156
(2011/11/01)
-
- Chemistry of lapachol - Syntheses of some new biogenetically related naphthoquinones, naphthoquinone dimers, naphthaquinoxaline and naphtha-azaquinoxaline derivatives from lapachol
-
The present short review focus on chemical transformations of lapachol to a large number of biogenetically related lapachol conegeners, dimers and heterocyclic analogues that have been achieved in our laboratory during more than two decades. Conversion of lapachol to stenocarpoquinone-B, rhinacanthin-A, β-(l-hydroxyisopropanyl)-dihydrofurano-1,2-naphthoquinone, stenocarpoquinone-A, dehydro-α-lapachone and dehydro-β-lapachone by the reaction with m-chloroperbenzoic acid; dehydroiso-α-lapachone, dehydroiso-β-lapachone, dehydro-α-lapachone, α-lapachone and β-lapachone by the reaction with aqueous NaNO2 and glacial AcOH; adenophyllone, quadrllone and dehydro-α-lapachone by the reaction with boiling pyridine; naphthaquinoxaline and naphtha-azaquinoxaline derivatives by the reaction with 1,2-diamines and dialkyltin dilapacholates by the reaction with dialkyltin diisopropoxides have been accomplished. Notably the syntheses of rhinacanthin-A, β-(1-hydroxyisopropanyl)-dihydrofurano-1,2-naphthoquinone, dehydroiso-α-lapachone, dehydroiso-β-lapachone, adenophyllone and quadrllone have been reported for the first time from our group starting from lapachol. The synthesis of novel naphthaquinoxaline and azaquinoxaline derivatives from lapachol has been additional interesting results of this investigation.
- Singh, Pahup,Krishna, Vivek,Khandelwal, Poonam,Sharma, Kuldeep K.,Sharma
-
experimental part
p. 85 - 95
(2011/07/30)
-
- Antiproliferative activity of synthetic naphthoquinones related to lapachol. First synthesis of 5-hydroxylapachol
-
A series of 5-hydroxy-1,4-naphthoquinones analogues was synthesized from juglone (6) and their antiproliferative activity against a representative panel of six human solid tumor cell lines has been investigated. The 2,5-dihydroxy-3-(3-methylbut-2-enyl)naphthalene-1,4-dione (4) and 2,3-dihydro-5-hydroxy-2-(prop-1-en-2-yl)naphtho[2,3-b]furan-4,9-dione (27) were the most potent antiproliferative agents with GI50 values of 0.42-8.1 and 0.80-2.2 μM, respectively. The results provide insight into the correlation between some structural properties of 5-hydroxynaphthoquinones and their antiproliferative activity.
- Bonifazi, Evelyn L.,Ríos-Luci, Carla,León, Leticia G.,Burton, Gerardo,Padrón, José M.,Misico, Rosana I.
-
scheme or table
p. 2621 - 2630
(2010/06/16)
-
- Environmentally benign, one-pot synthesis of pyrans by domino Knoevenagel/6π-electrocyclization in water and application to natural products
-
In water medium, environmentally benign, facile, and efficient synthesis of pyrans was achieved in good yields by the reactions of a variety of cyclic 1,3-dicarbonyls with several α,β-unsaturated aldehydes. The key strategy was a formal [3+3] cycloaddition by domino Knoevenagel/6π- electrocyclization. This methodology was applied to the synthesis of biologically interesting pyranocoumarin, pyranoquinolinone, and pyranonaphthoquinone derivatives along with selected natural and non-natural products. The Royal Society of Chemistry 2010.
- Jung, Ene Jin,Park, Byung Ho,Lee, Yong Rok
-
experimental part
p. 2003 - 2011
(2011/02/19)
-
- NOVEL IDO INHIBITORS AND METHODS OF USE THEREOF
-
Novel indolearaine 2, 3-dioxygenase (IDO) inhibitors, compositions comprising the same, and methods of use thereof are disclosed.
- -
-
Page/Page column 24-28
(2008/12/07)
-
- Trypanosoma cruzi: Activities of lapachol and α- and β-lapachone derivatives against epimastigote and trypomastigote forms
-
Derivatives of natural quinones with biological activities, such as lapachol, α- and β-lapachones, have been synthesized and their trypanocidal activity evaluated in vitro in Trypanosoma cruzi cells. All tested compounds inhibited epimastigote growth and trypomastigote viability. Several compounds showed similar or higher activity as compared with current trypanocidal drugs, nifurtimox and benznidazole. The results presented here show that the anti-T. cruzi activity of the α-lapachone derivatives can be increased by the replacement of the benzene ring by a pyridine moiety. Free radical production and consequently oxidative stress through redox cycling or production of electrophilic metabolites are the potential biological mechanism of action for these synthetic quinones.
- Salas, Cristian,Tapia, Ricardo A.,Ciudad, Karina,Armstrong, Veronica,Orellana, Myriam,Kemmerling, Ulrike,Ferreira, Jorge,Maya, Juan Diego,Morello, Antonio
-
p. 668 - 674
(2008/09/17)
-
- Synthesis and anti-Trypanosoma cruzi activity of derivatives from nor-lapachones and lapachones
-
New naphthoquinone derivatives were synthesized and assayed against bloodstream trypomastigote forms of Trypanosoma cruzi, the etiological agent of Chagas' disease. The compounds were rationalized based on hybrid drugs and appear as important compounds ag
- da Silva Junior, Eufranio N.,de Souza, Maria Cecilia B.V.,Fernandes, Michelle C.,Menna-Barreto, Rubem F.S.,Pinto, Maria do Carmo F.R.,de Assis Lopes, Francisco,de Simone, Carlos Alberto,Andrade, Carlos Kleber Z.,Pinto, Antonio V.,Ferreira, Vitor F.,de Castro, Solange L.
-
p. 5030 - 5038
(2008/12/21)
-
- Radermachol and naphthoquinone derivatives from Tecomella undulata: Complete 1H and 13C NMR assignments of radermachol with the aid of computational 13C shift prediction
-
Petroleum ether extract of the heartwood of Tecomella undulata affords radermachol, an unusual rare pigment and 2-isopropenylnaphtho[2,3-b]furan-4,9- quinone along with lapachol, tecomaquinone-I, dehydro-α-lapachone, α-lapachone, β-lapachone, cluytyl ferulate, stigmasterol and β-sitosterol. Radermachol and 2-isopropenylnaphtho [2,3-b]furan-4,9-quinone are being reported for the first time from genus Tecomella. Complete assignments of 1H and 13C NMR signals of polyketide, radermachol 1, have been achieved by the 13C NMR chemical shift prediction using ab initio MO and DFT/GIAO methods in addition to 2D-NMR techniques.
- Singh, Pahup,Khandelwal, Poonam,Hara, Noriyuki,Asai, Teigo,Fujimoto, Yoshinori
-
experimental part
p. 1865 - 1870
(2009/05/27)
-
- Cytotoxic germacrane-type sesquiterpenes, pimarane-type diterpenes, and a naphthalene derivative from Wollastonia biflora
-
Phytochemical investigation of the whole plants of Wollastonia biflora led to the isolation and identification of three new germacrane-type sesquiterpenes (1-3), two new pimarane-type diterpenes (4, 5), and a new naphthalene glycoside (6), along with 11 known compounds. Their structures were characterized on the basis of spectroscopic analyses and chemical methods. Compounds 1, 2, and 3 showed significant cytotoxic activity against me growth of hepatocellular carcinoma BEL-7402 cells in vitro.
- Chen, Wenliang,Tang, Weidong,Zhang, Rujun,Lou, Liguang,Zhao, Weimin
-
p. 567 - 570
(2008/02/13)
-
- Synthesis and pharmacophore modeling of naphthoquinone derivatives with cytotoxic activity in human promyelocytic leukemia HL-60 cell line
-
Catalyst/HypoGen pharmacophore modeling approach and three-dimensional quantitative structure-activity relationship (3D-QSAR)/comparative molecular similarity indices analysis (CoMSIA) methods have been successfully applied to explain the cytotoxic activity of a set of 51 natural and synthesized naphthoquinone derivatives tested in human promyelocytic leukemia HL-60 cell line. The computational models have facilitated the identification of structural elements of the ligands that are key for antitumoral properties. The four most salient features of the highly active β-cycled-pyran-1,2-naphthoquinones [0.1 μM 50 0.6 μM] are the hydrogen-bond interactions of the carbonyl groups at C-1 (HBA1) and C-2 (HBA2), the hydrogen-bond interaction of the oxygen atom of the pyran ring (HBA3), and the interaction of methyl groups (HYD) at the pyran ring with a hydrophobic area at the receptor. The moderately active 1,4-naphthoquinone derivatives accurately fulfill only three of these features. The results of our study provide a valuable tool in designing new and more potent cytotoxic analogues.
- Pérez-Sacau, Elisa,Díaz-Peńate, Raquel G.,Estévez-Braun, Ana,Ravelo, Angel G.,García-Castellano, Jose M.,Pardo, Leonardo,Campillo, Mercedes
-
p. 696 - 706
(2008/02/01)
-
- A concise route for the synthesis of pyranonaphthoquinone derivatives
-
An efficient synthesis of pyranonaphthoquinones is achieved by ethylenediamine diacetate-catalyzed reactions of 4-hydroxy-2-quinolones with a variety of α,β-unsaturated aldehydes in moderate yields. This method provides a rapid entry into biologically interesting α-lapachone derivatives with a variety of substituents on the pyran ring. Georg Thieme Verlag Stuttgart.
- Lee, Yong Rok,Choi, Jung Hyun,Trinh, Dinh Thi Lan,Kim, Nam Woo
-
p. 3026 - 3034
(2007/10/03)
-
- Conversion of lapachol to array of furano and pyranonaphthoquinone congeners
-
Chemical conversion of lapachol to α-lapachone, β-lapachone, dehydro-α-lapachone, dehydroiso-α-lapachone and dehydroiso-β- lapachone by reaction with aqueous NaNO2 and glacial AcOH; rhinacanthin-A, stenocarpoquinone-A, stenocarpoquinone-B and its isomer by reaction with meta-chloroperbenzoic acid at 0° for 30 min and dehydro-α-lapachone and dehydro-β-lapachone at 25° for 4 h respectively and di- and tribromo derivatives by reaction with Br2 in chloroform has been reviewed. In most of these reactions prenyl chain cyclises into an oxygen function to give a number of furano and pyrano-naphthoquinone derivatives. Some of these naphthoquinones co-occur with lapachol in the same plant species.
- Krishna, Vivek,Lamba, Jyoti,Singh, Pahup
-
p. 1039 - 1044
(2007/10/03)
-
- Efficient synthesis of biologically interesting dehydro-α-lapachone and α-lapachone
-
An efficient synthesis of biologically active dehydro-α-lapachone and α-lapachone has been carried out starting from 2-hydroxy-1,4- naphthoquinone by a tandem Knoevenagel-electrpcyclic reaction.
- Yong, Rok Lee,Won, Kyong Lee
-
p. 4537 - 4543
(2007/10/03)
-
- Monoarylhydrazones of α-lapachone: Synthesis, chemical properties and antineoplastic activity
-
The biological activities of the naphthoquinones lapachol, extracted from trees of the genus Tabebuia and its cyclization products α and β-lapachone, have been intensively studied. Giving continuity to the research about new derivatives obtained from the reaction of these naphthoquinones with amino-containing reagents, a series of arylhydrazones of α-lapachone was synthesized and their antineoplastic activity was evaluated. This new structure is based on the great electrophilicity of 1,4-quinoidal carbonyl groups towards reagents containing nitrogen as nucleophilic centers, such as arylhydrazines. The products were assayed by the National Cancer Institute (NCI, USA) and their binding to DNA, redox properties and QSAR studies were also determined.
- Renou, Sergio Gaston,Asis,Abasolo,Bekerman,Bruno
-
p. 690 - 695
(2007/10/03)
-
- Inhibitory effects of lapachol derivatives on epstein-barr virus activation
-
Sixteen derivatives (2-17) synthesized from the naphthoquinone lapachol (1), were tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), as a test for potential cancer chemopreventive agents. They exhibited a variety of inhibitory activities from very high to moderate, which allow us to suggest structure-activity relationships. Ten of these derivatives are reported for the first time, their structures being thoroughly determined by spectroscopic methods.
- Sacau, Elisa Perez,Estevez-Braun, Ana,Ravelo, Angel G.,Ferro, Esteban A.,Tokuda, Harunkuni,Mukainaka, Teruo,Nishino, Hoyoku
-
p. 483 - 488
(2007/10/03)
-
- Synthesis of lapachol derivatives and their antibacterial activity
-
Several lapachol derivatives were synthesized from lapachol and tested for their antibacterial activity.
- Vasanth, Saradha,Jayakaran,Raj, Victor Paul,Srinivasan
-
p. 765 - 767
(2007/10/03)
-
- Indium(III) bromide-catalyzed preparation of dihydropyrimidinones: Improved protocol conditions for the Biginelli reaction
-
Indium(III) bromide efficiently catalyzes the three-component coupling of β-keto esters, aldehydes and urea (or thiourea) to afford the corresponding dihydropyrimidinones. This new protocol for the Biginelli reaction includes the following important features: produces excellent yields, allows the recycling of catalyst with no loss in its activity, and leads to zero-discharge during the process. The reaction of ethyl acetoacetate, salicylaldehyde and thiuourea produced 13-ethoxycarbonyl-9-methyl-11-thioxo-8-oxa-10,12-diazatricyclo [7.3.1.02,7]-trideca-2,4-6-triene, which had its crystal structure determined by X-ray crystallography.
- Fu, Nan-Yan,Yuan, Yao-Feng,Cao, Zhong,Wang, Shan-Wei,Wang, Ji-Tao,Peppe, Clovis
-
p. 4801 - 4807
(2007/10/03)
-
- Chemical transformation of lapachol to dehydroiso-α-lapachone and related quinones
-
Chemical transformation of lapachol to dehydroiso-α-lapachone, dehydroiso-β-lapachone, α-lapachone, β-lapachone and dehydro-α-lapachone in a single step synthesis by reaction with aqueous NaNO2 and glacial AcOH and to di- and tri-bromo derivatives by reaction with Br2 in CHCl3 has been achieved. Notably dehydroiso-α-lapachone and dehydroiso-β-lapachone have been obtained from lapachol for the first time.
- Singh,Jain,Krishna
-
-
- Radermachera xylocarpa: The highly efficient source of lapachol and synthesis of its derivatives
-
Isolation and characterization of the major chemical constituents from the stem bark of Radermachera xylocarpa. Chloroform extract of the powdered stem bark contains mainly two components: one is lapachol (91.2%) and second is α-lapachone (5.0%), which are reported herewith first time from this plant, in good quantity and purity.
- Shetgiri,Kokitkar,Sawant
-
p. 133 - 135
(2007/10/03)
-
- Selective Aromatic Reduction in Pyranonaphthoquinone Systems
-
The solvent dependence in selective hydrogenation of pyranonaphthoquinones was investigated.It was found that the aromatic ring of these compounds can be hydrogenated at low pressure to the corresponding homologous benzoquinone derivatives.A free quinoidal ring or a quinol moiety is necessary for the reduction to proceed in this way.
- Ferreira, Vitor F.,Pinto, Antonio V.,Pinto, Maria C. R. F.,Silva, Mauricio M.
-
p. 182 - 191
(2007/10/02)
-
- Polyphosphoric acid Catalysed Transformation of Certain o-Hydroxy-alkenylated Naphthoquinones
-
Polyphosphoric acid transforms lapachol methyl ether (II) into β-lapachone (III), lapachol (I) into α- and β-lapachones (VII and III), lomatiol (IV) into iso-α-lapachone (VIII) and dehydro-α-lapachone (IX), and dihydroxyhydrolapachol (V) into 3'-hydroxy-β-lapachone (X).All the products obtained are naturally occurring compounds.Reaction of 2-hydroxy-3-(2-methylprop-1-enyl)-1,4-naphthoquinone (VI) furnishes 2,2-dimethyl-2,3,4,5-tetrahydro-4,5-dioxonaphthofuran (XI).
- Kapoor, N. K.,Gupta, R. B.,Khanna, R. N.
-
p. 251 - 252
(2007/10/02)
-