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

作者：Kumar Lalit; Sarswat Amit; Lal Nand; Jain Ashish; Kumar Sumit; Kumar S T V S Kiran; Maikhuri Jagdamba P; Pandey Atindra K; Shukla Praveen K; Gupta Gopal; Sharma Vishnu L^*

来源：Bioorganic & Medicinal Chemistry Letters, 2011, 21(1): 176-181.

DOI：10.1016/j.bmcl.2010.11.042

• Spermicides
• Antitrichomonas
• Anticandida
• Fluoxetine
• Nonoxynol-9

We designed a series of 25 3-(azol-1-yl)phenylpropanes which yielded 10 compounds (3, 4, 7, 8, 13, 14, 19, 21, 23, 26) that irreversibly immobilized 100% human sperm at 1% (w/v) concentration in 60 s; 12 compounds (8, 9, 15, 16, 19-21, 23-25, 27, 28) that showed potent microbicidal activity at 12.5-50 mu g/mL against Trichomonas vaginalis; and 17 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 mu g/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.

• 出版日期2011-1