Molecules, Vol. 25, Pages 793: Metronidazole and Secnidazole Carbamates: Synthesis, Antiprotozoal Activity, and Molecular Dynamics Studies

Molecules, Vol. 25, Pages 793: Metronidazole and Secnidazole Carbamates: Synthesis, Antiprotozoal Activity, and Molecular Dynamics Studies Molecules doi: 10.3390/molecules25040793 Authors: Rocha-Garduño Hernández-Martínez Colín-Lozano Estrada-Soto Hernández-Núñez Prieto-Martínez Medina-Franco Chale-Dzul Moo-Puc Navarrete-Vázquez We prepared a series of 10 carbamates derivatives based on two common antiprotozoal drugs: metronidazole (1–5) and secnidazole (6–10). The compounds were tested in vitro against a set of two amitochondriate protozoa: Giardia duodenalis and Trichomonas vaginalis. Compounds 1–10 showed strong antiprotozoal activities, with potency values in the low micromolar-to-nanomolar range, being more active than their parent drugs. Metronidazole carbamate (1) was the most active of the series, with nanomolar activities against G. duodenalis (IC50 = 460 nM) and T. vaginalis (IC50 = 60 nM). The potency of compound 1 was 10 times greater than that of metronidazole against both parasites. None of compounds showed in vitro cytotoxicity against VERO cells tested at 100 µM. Molecular dynamics of compounds 1–10, secnidazole, and metronidazole onto the ligand binding site of pyruvate–ferredoxin oxidoreductase of T. vaginalis and the modeled -tubulin of G. duodenalis revealed putative molecular interactions with key residues in the binding site of...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research