Hum. Reprod. Advance Access originally published online on November 17, 2006
Human Reproduction 2007 22(3):708-716; doi:10.1093/humrep/del448
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Novel disulphide esters of carbothioic acid as potent, non-detergent spermicides with low toxicity to Lactobacillus and HeLa cells in vitro
1 Division of Endocrinology 2 Division of Medicinal Chemistry 3 Division of Pharmaceutics and 4 Electron Microscopy Unit, Central Drug Research Institute, Lucknow, Uttar Pradesh, India
5 To whom correspondence should be addressed at: Division of Endocrinology, Central Drug Research Institute, Chhattar Manzil, PO Box 173, Lucknow 226001, Uttar Pradesh, India. E-mail: gupta.gopal{at}rediffmail.com
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 
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 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 EC50 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.
Key words: contraception/non-detergent spermicides/spermicidal activity/selective toxicity
Submitted on August 2, 2006; resubmitted on October 10, 2006; accepted on October 19, 2006.