{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T02:57:26Z","timestamp":1755226646122,"version":"3.43.0"},"reference-count":49,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp; Biodiversity"],"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Protozoal pathogens <jats:italic>Trichomonas vaginalis<\/jats:italic> and <jats:italic>Tritrichomonas foetus<\/jats:italic> are the causative agents of sexually transmitted diseases like trichomoniasis among humans and cattle, respectively. Metronidazole (a nitroimidazole\u2010based 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\u20107\u2010chloroquinoline hybrids, along with their preliminary screening against different strains of <jats:italic>T. vaginalis<\/jats:italic> and <jats:italic>T. foetus<\/jats:italic>. Most compounds showed moderate to good activities, with two of the most active compounds exhibiting minimum inhibitory concentrations (IC<jats:sub>50s<\/jats:sub>) of 3.9 and 2.9\u00a0\u00b5M against <jats:italic>T. vaginalis<\/jats:italic> and <jats:italic>T. foetus<\/jats:italic>, 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 IC<jats:sub>50<\/jats:sub> concentrations effective against parasite growth. Additionally, further evaluations revealed no inhibitory activity against fungi or bacteria, highlighting their specificity as anti\u2010protozoal agents.<\/jats:p>","DOI":"10.1002\/cbdv.202500062","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T18:46:49Z","timestamp":1743706009000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design and Synthesis of Nitroimidazole\u2010Quinoline Derivatives as Potential Therapeutics Specifically against Sexually\u2010Transmitted Anaerobic Protozoal Pathogens"],"prefix":"10.1002","author":[{"family":"Shalini","sequence":"first","affiliation":[{"name":"Department of Chemistry Guru Nanak Dev University  Amritsar India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shefali","family":"Chowdhary","sequence":"additional","affiliation":[{"name":"Department of Chemistry Guru Nanak Dev University  Amritsar India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirkwood M.","family":"Land","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences University of the Pacific  Stockton California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina C.","family":"Tam","sequence":"additional","affiliation":[{"name":"United States Department of Agriculture, Foodborne Toxin Detection and Prevention Research Unit Agricultural Research Service  Albany California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong H.","family":"Kim","sequence":"additional","affiliation":[{"name":"United States Department of Agriculture, Foodborne Toxin Detection and Prevention Research Unit Agricultural Research Service  Albany California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amit","family":"Anand","sequence":"additional","affiliation":[{"name":"Department of Chemistry Khalsa College  Amritsar India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6164-7161","authenticated-orcid":false,"given":"Vipan","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Chemistry Guru Nanak Dev University  Amritsar India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,4,15]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"World Health Organization Sexually Transmitted Infections (STIs) Available online:https:\/\/www.who.int\/news\u2010room\/factsheets\/detail\/sexually\u2010transmitted\u2010infections\u2010(stis) (accessed 20 December 2024)."},{"key":"e_1_2_8_3_1","unstructured":"World Health Organization Global Health Sector Strategies on HIV Viral Hepatitis and STIs for 2022\u20132030 Available online:https:\/\/www.who.int\/publications\/i\/item\/9789240053779(accessed 20 December 2024)."},{"key":"e_1_2_8_4_1","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1038\/s41564-022-01177-x","article-title":"Sexually Transmitted Infections and Female Reproductive Health","volume":"7","author":"Van Gerwen O. 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C.","year":"2007","journal-title":"Clinical Infectious Diseases"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.idc.2013.06.003","article-title":"Trichomoniasis","volume":"27","author":"Meites E.","year":"2013","journal-title":"Infectious Disease Clinics of North America"},{"key":"e_1_2_8_8_1","first-page":"113","article-title":"A Trich\u2010y Question","volume":"40","author":"Hoots B. 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Implications for Nitroimidazole Toxicity and Resistance","volume":"72","author":"Leitsch D.","year":"2009","journal-title":"Molecular Microbiology"},{"key":"e_1_2_8_42_1","first-page":"34572","article-title":"Trifluoromethyl Alcohols and Their Derivatives are Inhibitors of Thioredoxin Reductase and Kill Entamoeba Histolytica","volume":"282","author":"Leitsch D.","year":"2007","journal-title":"Journal of Biological Chemistry"},{"key":"e_1_2_8_43_1","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1042\/BJ20121798","article-title":"Entamoeba histolytica: Identification of Thioredoxin\u2010targeted Proteins and Analysis of Serine Acetyltransferase\u20101 as a Prototype Example","volume":"451","author":"Schlosser S.","year":"2013","journal-title":"Biochemical Journal"},{"key":"e_1_2_8_44_1","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/s10822-010-9349-1","article-title":"Towards the Comprehensive, Rapid, and Accurate Prediction of the Favorable Tautomeric States of Drug\u2010Like Molecules in Aqueous Solution","volume":"24","author":"Greenwood J. 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