Naphthoquinone-based Hydrazone Hybrids: Synthesis and Potent Activity Against Cancer Cell Lines

Author(s): Délis Galváo Guimaráes, Arlan de Assis Gonsalves, Larissa Araújo Rolim, Edigênia Cavalcante Araújo, Victória Laysna dos Anjos Santos, Maria Francilene Souza Silva, Fátima de Cássia Evangelista de Oliveira, Marcília Pinheiro da Costa, Claudia Pessoa, Marília Oliveira Fonseca Goulart, Thaissa Lucio Silva, Danyelle Cândido Santos, Cleônia Roberta Melo Araújo*

Journal Name: Medicinal Chemistry

Volume 17 , Issue 9 , 2021

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Graphical Abstract:


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 β- lapachones (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.

Keywords: β-lapachone, α-lapachone, antitumor, cancer cell lines, isoniazide and hydralazine molecular hybridization.

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Article Details

Year: 2021
Published on: 17 August, 2020
Page: [945 - 955]
Pages: 11
DOI: 10.2174/1573406416666200817164308
Price: $65

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