Azole–carbodithioate hybrids as vaginal anti-Candida contraceptive agents: Design, synthesis and docking studies

• Published in: European journal of medicinal chemistry 2013-12, Vol.70, p.68-77
• Main Authors: Kumar, Lalit, Lal, Nand, Kumar, Vikash, Sarswat, Amit, Jangir, Santosh, Bala, Veenu, Kumar, Lokesh, Kushwaha, Bhavana, Pandey, Atindra K., Siddiqi, Mohammad I., Shukla, Praveen K., Maikhuri, Jagdamba P., Gupta, Gopal, Sharma, Vishnu L.
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Anti-Candida; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Antiprotozoal Agents - chemical synthesis; Antiprotozoal Agents - chemistry; Antiprotozoal Agents - pharmacology; Azoles - chemical synthesis; Azoles - chemistry; Azoles - pharmacology; Candida - drug effects; Carbon disulfide; Dithiocarbamate; Docking; Drug Design; Escherichia coli - drug effects; HeLa Cells; Humans; Imidazole; Klebsiella pneumoniae - drug effects; Microbial Sensitivity Tests; Models, Molecular; Molecular Structure; Parasitic Sensitivity Tests; Pseudomonas aeruginosa - drug effects; Spermicides; Staphylococcus aureus - drug effects; Sulfhydryl Compounds - chemical synthesis; Sulfhydryl Compounds - chemistry; Sulfhydryl Compounds - pharmacology; Trichomonas vaginalis - drug effects
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2013.09.007

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. [Display omitted] •Azole and carbodithioate hybrids were synthesized.•Compounds were evaluated for spermicidal/microbicidal activity.•Sixteen compounds were dually active against sperm and Candida.•Promising compounds were safer than Nonoxynol-9.•Docking study provided guidelines for designing anti-Candida agents.