Novel disulphide esters of carbothioic acid as potent, non-detergent spermicides with low toxicity to Lactobacillus and HeLa cells in vitro

Hum Reprod. 2007 Mar;22(3):708-16. doi: 10.1093/humrep/del448. Epub 2006 Nov 17.

Abstract

Background: The design, synthesis, characterization and evaluation of a novel series of non-detergent spermicides has led to the discovery of two unique molecules (DSE-36 and DSE-37) that were approximately 25 times more potent spermicides than nonoxynol-9 (N-9).

Methods: Normal human spermatozoa were used to assess the spermicidal activity (Sander-Cramer Assay), the effect on sperm-membrane integrity [hypo-osmotic swelling test (HOST)], supravital staining and scanning electron microscopy (SEM) and the induction of apoptosis [fluorescein isothiocyanate (FITC) Annexin-V and JC-1 labelling using flow cytometry] by the new class of compounds. HeLa and Lactobacillus cultures were used to assess the cytotoxicity of compounds and their compatibility to normal vaginal flora, respectively.

Results: Compounds DSE-36 and DSE-37 exhibited a strong spermicidal activity [minimum effective concentration (MEC) = 0.002%], which was approximately 25 times more potent than that of N-9 and Sapindus saponins (MEC = 0.05%). As compared with surfactants, DSE-36 and DSE-37 were found to be safer at MEC towards the growth and survival of Lactobacilli and HeLa cells in vitro and to have a milder effect on sperm plasma membrane. At EC(50) both induced apoptosis in sperm cells as characterized by increased labelling with Annexin-V and decreased polarization of sperm mitochondria.

Conclusion: Preliminary studies have revealed that in sharp contrast to the non-specific surfactant action of N-9, DSE-36 and DSE-37 have a highly potent, mechanism-based, detrimental action on human sperm. The unique ability of these non-detergent molecules to selectively kill sperm and spare Lactobacilli and HeLa cells at MEC values much lower than that required for N-9 indicates their potential as superior ingredients for formulation into microbicidal contraceptives.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Survival / drug effects
  • Disulfides / pharmacology*
  • Flow Cytometry
  • HeLa Cells / drug effects
  • Humans
  • Lactobacillus acidophilus / drug effects*
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Microscopy, Electron, Scanning
  • Nonoxynol / pharmacology*
  • Spermatocidal Agents / pharmacology*
  • Spermatozoa / drug effects*
  • Spermatozoa / ultrastructure

Substances

  • DSE-36 compound
  • DSE-37 compound
  • Disulfides
  • Spermatocidal Agents
  • Nonoxynol