Executive Summary : | Leishmaniasis is a complex communicable disease affecting poor people in sub-tropical and tropical areas of the globe. It is one of the top ten neglected tropical diseases, with over 12 million infected people, 0.9 to 1.6 million new cases each year, between 20,000 and 30,000 deaths, and 350 million people at risk of infection. Leishmaniasis is caused by a single-celled protist from the order Kinetoplastida transmitted by phlebotomine sandflies. The disease can be characterized by clinical manifestations among infected individuals, including Visceral Leishmaniasis (VL), Cutanian Leishmaniasis (CL), Mucocutaneous ML, and Postkala-Azar dermal leishmaniasis (PKDL). Leishmaniasis chemotherapy mainly relies on decade-old drugs due to the lack of a prophylactic or preventive effective vaccine. Despite severe adverse effects, pentavalent antimonials amphotericin B, Pentamidines, and paromomycin have been used for treatment. Chromones, oxygen-containing heterocyclic compounds with a benzoannelated γ-pyrone ring, are a group of secondary metabolites from plants. Carboxamide derivatives have shown potential inhibitors of various FDA-approved drugs, and recent literature surveys have improved the efficacy of these molecules. Urgent development of new anti-leishmanial agents with high potential, improved therapeutic profiles, reduced toxicity, and efficacy against wild and resistant strains of Leishmania is urgently needed. The proposed proposal aims to design, synthesize, characterization, anti-leishmanial assessment, and molecular target identification of thiochromene carboxamide analogs using molecular hybridization method. |