Design and Synthesis of Nitroimidazole‐Quinoline Derivatives as Potential Therapeutics Specifically against Sexually‐Transmitted Anaerobic Protozoal Pathogens

Protozoal pathogens Trichomonas vaginalis and Tritrichomonas foetus are the causative agents of sexually transmitted diseases like trichomoniasis among humans and cattle, respectively. Metronidazole (a nitroimidazole-based entity) has been used as the preferred drug to treat protozoal infections for the past few years. However, the emergence of resistance has prompted researchers to further explore the nitroimidazole core to overcome its limitations while improving efficacy. Herein, we describe the synthesis of a series of nitroimidazole derivatives and nitroimidazole-7-chloroquinoline hybrids, along with their preliminary screening against different strains of T. vaginalis and T. foetus. Most compounds showed moderate to good activities, with two of the most active compounds exhibiting minimum inhibitory concentrations (IC_50s) of 3.9 and 2.9 µM against T. vaginalis and T. foetus, respectively. Molecular docking studies revealed robust binding interactions of these compounds within the active site of thioredoxin reductase, reinforcing their potential as effective inhibitors. These compounds exhibited no mammalian cell cytotoxicity at IC₅₀ concentrations effective against parasite growth. Additionally, further evaluations revealed no inhibitory activity against fungi or bacteria, highlighting their specificity as anti-protozoal agents.