Design and synthesis of nitroimidazole-quinoline derivatives as potential therapeutics specifically against sexually-transmitted anaerobic protozoal pathogens

Authors: SHALINI, SHALINI - Guru Nanak Dev University; CHOWDHARY, SHELFALI - Guru Nanak Dev University; LAND, KIRKWOOD - University Of The Pacific; Tam, Christina; Kim, Jong Heon; ANAND, AMIT - Khalsa College; KUMAR, VIPAN - Guru Nanak Dev University

Submitted to: Chemistry and Biodiversity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/1/2025
Publication Date: 4/3/2025
Citation: Shalini, S., Chowdhary, S., Land, K.M., Tam, C.C., Kim, J., Anand, A., Kumar, V. 2025. Design and synthesis of nitroimidazole-quinoline derivatives as potential therapeutics specifically against sexually-transmitted anaerobic protozoal pathogens. Chemistry and Biodiversity. e202500062. https://doi.org/10.1002/cbdv.202500062.
DOI: https://doi.org/10.1002/cbdv.202500062

Interpretive Summary: Protozoal pathogens T. vaginalis and T. foetus are the causative agents of the sexually transmitted disease (STD) Trichomoniasis, among humans and cattle respectively. Metronidazole (a nitroimidazole based entity) is the most preferred drug to treat protozoal infections but increasing and emerging antibiotic resistance has driven the development of new drugs to combat this disease. We have developed a library of compounds based on the base structure of nitroimidazole core. Screening of this library of novel compounds with T. vagainalis and T. foetus for growth inhibition was performed. We show that some of the compounds (7b and 7d) were the most active in to inhibit/kill the different strains of T. vaginalis and T. foetus in the micromolar range. Additionally, none of these compounds affected probiotic organisms nor fungal or bacterial pathogens thus the growth inhibition seen with the parasites was specific.

Technical Abstract: Protozoal pathogens T. vaginalis and T. foetus are the causative agents of sexually transmitted disease (STD) Trichomoniasis, among humans and cattle respectively. Metronidazole (a nitroimidazole based entity) is the most preferred drug to treat protozoal infections for past few years. But the incidence of emerging resistance has led the researchers to further explore nitroimidazole core to combat its limitations while improving its efficacy. Herein describes the synthesis of a series of nitroimidazole derivatives and nitroimidazole-7-chloroquinoline hybrids along with their preliminary screening evaluation against different strains of T. vaginalis and T. foetus. Most of the compounds showed moderate to good activities, with the compounds 7b and 7d, proved to be the most active with IC50 values 3.9 and 2.9 'M against T. vaginalis and T. foetus respectively.