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

Eur J Med Chem. 2013:70:68-77. doi: 10.1016/j.ejmech.2013.09.007. Epub 2013 Sep 19.

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.

Keywords: Anti-Candida; Carbon disulfide; Dithiocarbamate; Docking; Imidazole; Spermicides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • 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
  • Drug Design*
  • Escherichia coli / drug effects
  • HeLa Cells
  • Humans
  • Klebsiella pneumoniae / drug effects
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Pseudomonas aeruginosa / drug effects
  • Staphylococcus aureus / drug effects
  • Sulfhydryl Compounds / chemical synthesis
  • Sulfhydryl Compounds / chemistry
  • Sulfhydryl Compounds / pharmacology*
  • Trichomonas vaginalis / drug effects

Substances

  • Anti-Bacterial Agents
  • Antifungal Agents
  • Antiprotozoal Agents
  • Azoles
  • Sulfhydryl Compounds