Imidazole Carbamates as a Promising Alternative for Treating Trichomoniasis: In Vitro Effects on the Growth and Gene Expression of .

Metronidazole (MTZ) is the most common drug used against () infections; however, treatment failures and high rates of recurrence of trichomoniasis have been reported, suggesting the presence of resistance in to MTZ. Therefore, research into new therapeutic options against infections has become increasingly urgent. This study investigated the trichomonacidal activity of a series of five imidazole carbamate compounds (AGR-1, AGR-2, AGR-3, AGR-4, and AGR-5) through in vitro susceptibility assays to determine the IC value of each compound. All five compounds demonstrated potent trichomonacidal activity, with IC values in the nanomolar range and AGR-2 being the most potent (IC 400 nM). To gain insight into molecular events related to AGR-induced cell death in , we analyzed the expression profiles of some metabolic genes in the trophozoites exposed to AGR compounds and MTZ. It was found that both AGR and MTZ compounds reduced the expression of the glycolytic genes (, , , and ) and genes involved in metabolism (, , , , , and ), suggesting that disturbing these key metabolic genes alters the survival of the parasite and that they probably share a similar mechanism of action. Additionally, the compounds showed low cytotoxicity in the Caco-2 and HT29 cell lines, and the results of the ADMET analysis indicated that these compounds have pharmacokinetic properties similar to those of MTZ. The findings offer significant insights that can serve as a basis for future in vivo studies of the compounds as a potential new treatment against .