Novel Spirooxindole Derivatives as Potential Non‐Detergent Type Spermicides

Abstract

AbstractThe aim of the present study is to explore the spermicidal potential of the synthetic spirooxindole derivatives and to examine the pathway behind the spermicidal action of the compounds. The in vitro spermicidal activities of the compounds were examined against human sperm by the modified Sander‐Cramer test. The pathway behind the spermicidal action of lead compounds was assessed by (a) hypo‐osmotic swelling test, (b) double fluoroprobe staining, (c) flowcytometric detection of apoptosis by FITC‐AnnexinV labelling, and (d) JC1 labelling. The haemolytic assay for topical toxicity of the compounds was carried out using rabbit erythrocytes. Two spirooxindole derivatives 4 a and 4 c were found to be most effective against human spermatozoa with MEC values of 500 μg/mL and 600 μg/mL lying in the range of standard spermicide Nonoxynol‐9 or N‐9 (MEC 550 μg/mL). The studies on the mechanism of action of the compounds unveiled that the compounds mediated sperm death were due to cellular apoptosis rather than general cell necrosis. The haemolysis assay assured the safeness of the lead molecules for topical usage. Thus, these spirooxindole derivatives may further be explored as new leads for the development of a non‐detergent type of topically applicable contraceptive formulation.