Substituted 1,5-naphthyridine derivatives as novel antileishmanial agents. Synthesis and biological evaluation

摘要

Visceral leishmaniasis is a parasitic disease that affects, among other areas, both sides of the Mediterranean Basin. The drugs classically used in clinical practice are pentavalent antimonials (Sbv) and amphotericin B, which are nephrotoxic, require parenteral administration, and increasing drug resistance in visceral leishmaniasis has been observed. These circumstances justify the search of new families of compounds to find effective drugs against the disease. Eukaryotic type I DNA topoisomerase (TopIB) has been found essential for the viability of the parasites, and therefore represents a promising target in the development of an antileishmanial therapy. In this search, heterocyclic compounds, such as 1,5-naphthyridines, have been prepared by cycloaddition reaction between N-(3-pyridyl)aldimines and acetylenes and their antileishmanial activity on promastigotes and amastigote-infected splenocytes of Leishmania infantum has been evaluated.