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


CONCLUSIONS
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.
Jain
R K
RK
Division of Endocrinology, Central Drug Research Institute, Lucknow, Uttar Padesh, India.
Maikhuri
J P
JP
Kiran Kumar
S T V S
ST
Sharma
V L
VL
Dwivedi
A K
AK
Mitra
K
K
Bajpai
V K
VK
Gupta
G
G
D002470:Cell Survival / Q000187:drug effects; D004220:Disulfides / Q000494:pharmacology*; D005434:Flow Cytometry; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D007779:Lactobacillus acidophilus / Q000187:drug effects*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008855:Microscopy, Electron, Scanning; D017137:Nonoxynol / Q000494:pharmacology*; D013089:Spermatocidal Agents / Q000494:pharmacology*; D013094:Spermatozoa / Q000187:drug effects* / Q000648:ultrastructure
C519273:DSE-36 compound; C519274:DSE-37 compound; D004220:Disulfides; D013089:Spermatocidal Agents; D017137:Nonoxynol