Bioprospecting and synthesis of strategically designed molecules have been used in the search for drugs that can be in leishmaniasis. Hydrazones (HDZ) are promising compounds with extensive biological activities. The objective of this work was to perform in silico studies of hydrazones 1-5 and to evaluate their antileishmanial, cytotoxic and macrophage immunomodulatory potential in vitro. Hydrazones were subjected to prediction and molecular docking studies. Antileishmanial protocols on promastigotes and amastigotes of Leishmania amazonensis, cytotoxicity and macrophage immunomodulatory activity were performed. Hydrazones showed a good pharmacokinetic profile and hydrazone 3 and hydrazone 5 were classified as non-carcinogenic. Hydrazone 5 obtained the best conformation with trypanothione reductase. Hydrazone 1 and hydrazone 3 obtained the best mean inhibitory concentration (IC50) values for promastigotes, 4.4-61.96 μM and 8.0-58.75 μM, respectively. It also showed good activity on intramacrophagic amastigotes, with hydrazone 1 being the most active (IC50 = 6.79 μM) with selectivity index of 56. In cytotoxicity to macrophages hydrazone 3 was the most cytotoxic (CC50 = 256.3 ± 0,04 μM), while hydrazone 4 the least (CC50 = 1055.9 ± 0.03 μM). It can be concluded that the hydrazones revealed important pharmacokinetic and toxicological properties, in addition to antileishmania potential in reducing infection and infectivity in parasitized macrophages.
Keywords: ADMET; Hydrazones; Leishmaniasis; Molecular docking simulation.
Copyright © 2023. Published by Elsevier Ltd.