Quinazoline-Dihydropyrimidinone Hybrids as Potent Antichagasic and Antileishmanial Agents: Synthesis, Biological Evaluation and Molecular Docking Studies

This study presents the design and synthesis of a series of quinazoline-dihydropyrimidinone hybrid compounds with potential antichagasic and antileishmanial activities, addressed to fight against neglected tropical diseases (NTDs). All compounds were evaluated against the epimastigote and trypomastigote forms of Trypanosoma cruzi and the promastigote forms of Leishmania infantum, Leishmania braziliensis, Leishmania amazonensis, and Leishmania major. Among them, hybrids 7a and 7c showed significant activity against all parasites, surpassing the potency of the reference drugs miltefosine and benznidazole. Molecular docking simulation indicated strong interactions of hybrids 7a and 7c with key parasitic enzymes – such as cruzain from T. cruzi and sterol 14-alpha demethylase from L. infantum; dihydroorotate dehydrogenase from L. braziliensis; nucleoside diphosphate kinase (NDK) from L. amazonensis; and N-myristoyltransferase from L. major - which may underlie their observed in vitro efficacy.