title: Imidazole derivatives as possible microbicides with dual protection.
abstract: Twenty seven derivatives (2-28) of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethanol were synthesized and evaluated for anti-trichomonas, spermicidal and antifungal activities. Twenty six compounds were active against Trichomonas vaginalis at MIC ranging from 1-42 microM and seven compounds (9,18,19,22,24,26,28) immobilized 100% human spermatozoa at 1% concentration (w/v). Twenty three compounds (2,3,5,8-26,28) exhibited antifungal activity at 25-50 microg/mL concentration. Seven compounds (9,18,19,22,24,26,28) showed significant anti-trichomonas and spermicidal activities and also exhibited mild antifungal activity. All the compounds were highly safe towards human cervical cell line (HeLa) as shown by the cell-viability assay of HeLa cells at 200 microg/mL concentration, whereas nonoxynol-9 (N-9, the marketed spermicidal microbicide) was highly cytotoxic. Therefore, it may be concluded that introduction of the pharmacophore responsible for spermicidal activity into a proven anti-trichomonas structure may lead to a potent dual function microbicide better and safer than N-9.
authors.affiliation: Division of Medicinal and Process Chemistry, Central Drug Research Institute, Lucknow 226001, Uttar Pradesh, India.
authors.forename: Lalit
authors.initials: L
authors.lastname: Kumar
authors.forename: Amit
authors.initials: A
authors.lastname: Sarswat
authors.forename: Nand
authors.initials: N
authors.lastname: Lal
authors.forename: Vishnu L
authors.initials: VL
authors.lastname: Sharma
authors.forename: Ashish
authors.initials: A
authors.lastname: Jain
authors.forename: Rajeev
authors.initials: R
authors.lastname: Kumar
authors.forename: Vikas
authors.initials: V
authors.lastname: Verma
authors.forename: Jagdamba P
authors.initials: JP
authors.lastname: Maikhuri
authors.forename: Awanit
authors.initials: A
authors.lastname: Kumar
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Shukla
authors.forename: Gopal
authors.initials: G
authors.lastname: Gupta
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D005658:Fungi / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D008826:Microbial Sensitivity Tests; D013094:Spermatozoa / Q000187:drug effects; D014246:Trichomonas vaginalis / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D007093:Imidazoles; C029899:imidazole