Design and synthesis of 3-(azol-1-yl)phenylpropanes as microbicidal spermicides for prophylactic contraception

Abstract

We designed a series of twenty five 3-(azol-1-yl)phenylpropanes which yielded ten compounds (3,4,7,8,13,14,19,21,23,26) that irreversibly immobilized 100% human sperm at 1% (w/v) concentration in 60 seconds; twelve compounds (8,9,15,16,19-21,23-25,27,28) that showed potent microbicidal activity at 12.5-50 µg/mL against Trichomonas vaginalis; and seventeen compounds (3-11,13,15,19,21,23,26,28,30) that exhibited potent anticandida activity with minimum inhibitory concentration (MIC) of 12.5-50 µg/mL. Almost all the compounds exhibited high level of safety towards normal vaginal flora (Lactobacillus) and human cervical (HeLa) cells in comparison to the marketed spermicide nonoxynol-9 (N-9). All the biological activities were evaluated in vitro. Two compounds (4,8) with good safety profile exhibited multiple (spermicidal, antitrichomonas and anticandida) activities, warranting further lead optimization for furnishing a prophylactic vaginal contraceptive