title: Novel metronidazole-chalcone conjugates with potential to counter drug resistance in Trichomonas vaginalis.
abstract: Trichomoniasis is the most prevalent, curable sexually transmitted disease (STD), which increases risk of viral STDs and HIV. However, drug resistance has been developed by some strains of Trichomonas vaginalis against Metronidazole (MTZ), the FDA approved drug against trichomoniasis. In the present study twenty two chalcone hybrids of metronidazole have been synthesized in a quest to get new molecules with higher potential against metronidazole-resistant T. vaginalis. All new hybrid molecules were found active against T. vaginalis with varying levels of activity against MTZ-susceptible and resistant strains. Eight compounds (4a, 4c, 4d, 4e, 4f, 4h, 4q and 4s) were found as active as the standard drug with an MIC of 1.56 μg/ml against MTZ-susceptible strain. However, compounds 4e, 4h and 4m were 4-times more active than MTZ against drug-resistant T. vaginalis, amongst which 4e and 4h were most promising against both susceptible and resistant strains.
authors.affiliation: Department of Chemistry, H.N.B. Garhwal University (A Central University), Srinagar (Garhwal), Uttarakhand 246174, India; Department of Chemistry, University of Delhi, Delhi 110007, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Anthwal
authors.affiliation: Department of Chemistry, University of Delhi, Delhi 110007, India.
authors.forename: U Chinna
authors.initials: UC
authors.lastname: Rajesh
authors.affiliation: Department of Chemistry, H.N.B. Garhwal University (A Central University), Srinagar (Garhwal), Uttarakhand 246174, India. Electronic address: msmrawat@gmail.com.
authors.forename: M S M
authors.initials: MS
authors.lastname: Rawat
authors.affiliation: Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Bhavana
authors.initials: B
authors.lastname: Kushwaha
authors.affiliation: Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Jagdamba P
authors.initials: JP
authors.lastname: Maikhuri
authors.affiliation: Division of Medicinal & Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Vishnu L
authors.initials: VL
authors.lastname: Sharma
authors.affiliation: Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Gopal
authors.initials: G
authors.lastname: Gupta
authors.affiliation: Department of Chemistry, University of Delhi, Delhi 110007, India. Electronic address: dsrawat@chemistry.du.ac.in.
authors.forename: Diwan S
authors.initials: DS
authors.lastname: Rawat
mesh_terms: D000994:Antitrichomonal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002599:Chalcone / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008795:Metronidazole / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014247:Trichomonas Vaginitis / Q000188:drug therapy; D014246:Trichomonas vaginalis / Q000187:drug effects*
chemical_list: D000994:Antitrichomonal Agents; D008795:Metronidazole; D002599:Chalcone
keywords: Drug resistance; HeLa cell line; Metronidazole; Trichomonas vaginalis