title: Azole-carbodithioate hybrids as vaginal anti-Candida contraceptive agents: design, synthesis and docking studies.
abstract: Azole and carbodithioate hybrids were synthesized as alkyl 1H-azole-1-carbodithioates (7-27) and evaluated for spermicidal/microbicidal activities against human sperm, Trichomonas vaginalis and Candida species. Seventeen compounds (7-14, 16-18 and 20-25) showed spermicidal activity at MEC 1.0% (w/v) and permanently immobilized 100% normal human spermatozoa within ∼30 s. Seventeen compounds (7-11, 13-18 and 20-25) exhibited anti-Candida activity (IC50 1.26-47.69 μg/mL). All compounds were devoid of bactericidal activity against four bacterial strains (50.00 μg/mL) and antiprotozoal activity against Trichomonas vaginalis (200.00 μg/mL). Four promising compounds (10, 17, 20 and 22) have better safety profile as compared to Nonoxynol-9 (N-9). Docking study was done to visualize the possible interaction of designed scaffold with prospective receptor (Cyp51) of Candida albicans.
authors.affiliation: Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, UP, India.
authors.forename: Lalit
authors.initials: L
authors.lastname: Kumar
authors.forename: Nand
authors.initials: N
authors.lastname: Lal
authors.forename: Vikash
authors.initials: V
authors.lastname: Kumar
authors.forename: Amit
authors.initials: A
authors.lastname: Sarswat
authors.forename: Santosh
authors.initials: S
authors.lastname: Jangir
authors.forename: Veenu
authors.initials: V
authors.lastname: Bala
authors.forename: Lokesh
authors.initials: L
authors.lastname: Kumar
authors.forename: Bhavana
authors.initials: B
authors.lastname: Kushwaha
authors.forename: Atindra K
authors.initials: AK
authors.lastname: Pandey
authors.forename: Mohammad I
authors.initials: MI
authors.lastname: Siddiqi
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Shukla
authors.forename: Jagdamba P
authors.initials: JP
authors.lastname: Maikhuri
authors.forename: Gopal
authors.initials: G
authors.lastname: Gupta
authors.forename: Vishnu L
authors.initials: VL
authors.lastname: Sharma
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001393:Azoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects; D015195:Drug Design; D004926:Escherichia coli / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014246:Trichomonas vaginalis / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000981:Antiprotozoal Agents; D001393:Azoles; D013438:Sulfhydryl Compounds
keywords: Anti-Candida; Carbon disulfide; Dithiocarbamate; Docking; Imidazole; Spermicides