SÍNTESE, ATIVIDADE ANTILESHMANIA E CITOTÓXICA DE HIDRAZONAS DERIVADAS DE ALDEÍDOS NATURAIS

Leishmaniasis is endemic anthropozoonosis considered to be a severe public health problem. The treatment with pentavalent antimonials presents high toxicity motivating the search for effective and less toxic drugs. Hydrazones and N-acylhydrazones are functional groups that are prominent in Medicinal Chemistry, including as antiprotozoals. In this context, five hydrazones derived from the natural aldehydes were synthesized and the molecular structures were suitably determined to employ uni and bidimensional 1H and 13C NMR techniques. The antileishmanial activity of all hydrazones was determined against promastigote forms of Leishmania amazonensis, and the compounds HDZ-3, HDZ-4, and HDZ-5 showed the best results, with IC50 of 9.00, 38.10 and 26.30 µM, respectively. In the cytotoxic evaluation against RAW macrophages, HDZ-4 presented the least cytotoxic (CC50 = 222.24 µM) and the higher selectivity. Lipinski’s descriptors of the hydrazones were calculated, and the compounds HDZ-3 and HDZ-5 were more promising. These hydrazones are hybrids of natural aldehydes with drugs, the first is the result of the junction of the cinnamaldehyde with isoniazid, and the second of the vanillin with hydralazine. The results highlighted the Markush isonicotinoylhydrazone and phthalazinylhydrazone groups, molecular structures that are present in HDZ-3 and HDZ-5 and are therefore considered innovators in the development of antileishmanial drugs.