4707-33-9Relevant academic research and scientific papers
Photoconversion of β-Lapachone to α-Lapachone via a Protonation-Assisted Singlet Excited State Pathway in Aqueous Solution: A Time-Resolved Spectroscopic Study
Du, Lili,Li, Ming-De,Zhang, Yanfeng,Xue, Jiadan,Zhang, Xiting,Zhu, Ruixue,Cheng, Shun Cheung,Li, Xuechen,Phillips, David Lee
, p. 7340 - 7350 (2015)
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.
1,2,3-Triazole-, arylamino- and thio-substituted 1,4-naphthoquinones: Potent antitumor activity, electrochemical aspects, and bioisosteric replacement of C-ring-modified lapachones
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.
, p. 1608 - 1619 (2014)
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.
Naphthoquinone-based hydrazone hybrids: Synthesis and potent activity against cancer cell lines
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)
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.
α- and β-Lapachone Isomerization in Acidic Media: Insights from Experimental and Implicit/Explicit Solvation Approaches
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.
, p. 52 - 61 (2019/01/04)
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.
Ligand-based design, synthesis and biochemical evaluation of potent and selective inhibitors of Schistosoma mansoni dihydroorotate dehydrogenase
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)
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.
Design of hybrid molecules as antimycobacterial compounds: Synthesis of isoniazid-naphthoquinone derivatives and their activity against susceptible and resistant strains of Mycobacterium tuberculosis
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)
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.
Ruthenium-catalyzed C-H oxygenation of quinones by weak O-coordination for potent trypanocidal agents
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)
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.
LAPACHONE DERIVATIVES CONTAINING TWO REDOX CENTERS AND METHODS OF USE THEREOF
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Paragraph 00122, (2017/05/10)
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.
Discovery of quinone-directed antitumor agents selectively bioactivated by NQO1 over CPR with improved safety profile
Bian, Jinlei,Li, Xiang,Wang, Nan,Wu, Xingsen,You, Qidong,Zhang, Xiaojin
, p. 27 - 40 (2017/02/23)
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.
Synthesis and antitumor activity of selenium-containing quinone-based triazoles possessing two redox centres, and their mechanistic insights
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.
, p. 1 - 16 (2016/07/06)
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
