Synthesis and in vitro antiprotozoal evaluation of novel metronidazole-Schiff base hybrids

Abstract

Herein we report the synthesis of 21 novel small molecules inspired by metronidazole and Schiff base compounds. The compounds were evaluated against Trichomonas vaginalis and cross-screened against other pathogenic protozoans of clinical relevance. Most of these compounds were potent against T. vaginalis, exhibiting IC₅₀ values < 5 µM. Compound 20, the most active compound against T. vaginalis, exhibited an IC₅₀ value of 3.4 µM. A few compounds also exhibited activity against Plasmodium falciparum and Trypanosomal brucei brucei, with compound 6 exhibiting an IC₅₀ value of 0.7 µM against P. falciparum and compound 22 exhibiting an IC₅₀ value of 1.4 µM against T.b. brucei. Compound 22 is a broad-spectrum antiprotozoal agent, showing activities against all three pathogenic protozoans under investigation.

Keywords: Schiff base; Trichomonas vaginalis; antiprotozoal agent; metronidazole.