Design and synthesis of 3-(azol-1-yl)phenylpropanes as microbicidal spermicides for prophylactic contraception.
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 60s; 12 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 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 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.
Division of Medicinal and Process Chemistry, Central Drug Research Institute, CSIR, Lucknow 226 001, India.
Lalit
L
Kumar
Amit
A
Sarswat
Nand
N
Lal
Ashish
A
Jain
Sumit
S
Kumar
S T V S
ST
Kiran Kumar
Jagdamba P
JP
Maikhuri
Atindra K
AK
Pandey
Praveen K
PK
Shukla
Gopal
G
Gupta
Vishnu L
VL
Sharma
D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D003271:Contraceptive Agents, Female / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D015195:Drug Design; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007778:Lactobacillus / Q000187:drug effects; D011407:Propane / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D013089:Spermatocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D013329:Structure-Activity Relationship; D014246:Trichomonas vaginalis / Q000187:drug effects
D000890:Anti-Infective Agents; D000935:Antifungal Agents; D003271:Contraceptive Agents, Female; D013089:Spermatocidal Agents; D011407:Propane