Structure-enabled enhancement of potency in a metronidazole–benznidazole hybrid: design, synthesis, and evaluation of antitrypanosomal activity of a benzylamide-linked 5-nitroimidazole
Marco Edilson Freire Lima
Benznidazole (1) remains the primary antiparasitic drug used clinically for Chagas disease, underscoring the need to discover novel treatments targeting Trypanosoma cruzi (T. cruzi) infection. In this sense, the present work reports the in silico design of a novel hybrid (3) containing the 5-nitroimidazole core from the commercial antiparasitic drug metronidazole (2) and the N-benzylacetamide moiety from 1. These structural motifs were designed to target T. cruzi nitroreductase type I (TcNTR) fo