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.