Biological evaluation of thiazolopyrimidine derivatives as novel heterocyclic compounds against promastigote and amastigote-like forms of Leishmania infantum and Leishmania tropica

Abstract

Leishmaniasis is an underfunded neglected disease that affects 12 million people mainly living in developing countries. Herein, based on the data we obtained in our previous study, we designed and synthesized novel thiazolo[5,4-d]pyrimidine derivatives and evaluated their in vitro antileishmanial bio-activity. The compounds were synthesized, and their structures were elucidated. Then, their anti leishmanial activities were tested using both promastigote and amastigote-like forms of L. tropica and L. infantum parasites. Additionally, we evaluated the in silico physicochemical properties and the structure-activity relationships of the compounds. Compound 4-chloro-N-[5-(4-hydroxypiperidin-1 yl)thiazolo[5,4-d]pyrimidin-2-yl]benzamide (A1), with IC₅₀ values of 43.58 µM and 41.45 µM against L. tropica and L. infantum promastigotes, respectively, and 70.02 µM and 77.13 µM against L. tropica and L. infantum axenic amastigote-like forms, was found to be the most active compound in both assays. Compound A1 also exhibited the lowest iLogP value among the compounds, suggesting high passive gastrointestinal absorption. Based on both in vitro assays and in silico properties, compound A1 demonstrates significant anti-parasitic activity and serves as a promising lead for the development of new antileishmanial agents.