Synthesis, in vitro Antitrichomonal Activity, and Docking Study of N-[(4-substituted phenyl)-1,3-thiazol-2-yl]-4-substituted Benzenesulfonamides

Abstract

Infection by Trichomonas vaginalis has a high incidence/prevalence worldwide. It has been associated with a predisposition to cervical neoplasia or prostate cancer and an increased risk of acquisition of human papillomavirus (HPV) and human immunodeficiency virus (HIV). Besides, resistance to the drugs used for trichomoniasis treatment has increased in the last 30 years. Herein, thirteen phenylthiazolylbenzene sulfonamides were synthesized and evaluated for their in vitro activity against Trichomonas vaginalis. Among them, four derivatives showed higher anti-trichomonal activity than metronidazole (IC50 = 0.93 µM), while their cytotoxicity levels were not significant. These compounds were subject to molecular docking studies using Trichomonas vaginalis ferredoxin as target. The results revealed that the orientation of the nitro group of the active derivatives is toward [2Fe-2S], the cluster responsible for high reactive oxygen species generation. Finally, it was evident that the presence of a nitro group in the structure of the synthesized phenylthiazolylbenzene sulfonamides is essential for their trichomonicidal activity.