Thiosemicarbazones as promising candidates for the treatment of visceral leishmaniasis: advances and perspectives

Abstract

Objective: To gather the main information available in the literature on the advances, limitations, and prospects of using thiosemicarbazones as a leishmanicidal agent for Leishmania infantum, the cause of visceral leishmaniasis, addressing their chemical properties, mechanisms of action, and results of in vitro studies. Literature review: Visceral leishmaniasis (VL) is a neglected tropical disease with high morbidity and mortality. Conventional treatment includes drugs such as pentavalent antimonials, amphotericin B, miltefosine, pentamidine, and paromomycin. Despite their efficacy, these therapies have significant limitations, such as systemic toxicity, high cost, administration difficulties, and the emergence of resistant strains. Therefore, thiosemicarbazones (TSCs) have been investigated as promising alternatives. These versatile organic compounds are capable of structural modification, enhancing antiparasitic activity and reducing adverse effects. Studies report several mechanisms of action, including mitochondrial depolarization, interaction with parasite DNA, induction of apoptosis, and inhibition of essential proteins. In vitro assays demonstrate that TSC derivatives exhibit significant leishmanicidal activity, including against strains resistant to conventional therapy. Final considerations: According to the literature, thiosemicarbazones represent a promising alternative for the development of new treatments against VL, standing out as a relevant focus for future research.