Imidazole derivatives as possible microbicides with dual protection.
Twenty seven derivatives (2-28) of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethanol were synthesized and evaluated for anti-trichomonas, spermicidal and antifungal activities. Twenty six compounds were active against Trichomonas vaginalis at MIC ranging from 1-42 microM and seven compounds (9,18,19,22,24,26,28) immobilized 100% human spermatozoa at 1% concentration (w/v). Twenty three compounds (2,3,5,8-26,28) exhibited antifungal activity at 25-50 microg/mL concentration. Seven compounds (9,18,19,22,24,26,28) showed significant anti-trichomonas and spermicidal activities and also exhibited mild antifungal activity. All the compounds were highly safe towards human cervical cell line (HeLa) as shown by the cell-viability assay of HeLa cells at 200 microg/mL concentration, whereas nonoxynol-9 (N-9, the marketed spermicidal microbicide) was highly cytotoxic. Therefore, it may be concluded that introduction of the pharmacophore responsible for spermicidal activity into a proven anti-trichomonas structure may lead to a potent dual function microbicide better and safer than N-9.
Kumar
Lalit
L
Division of Medicinal and Process Chemistry, Central Drug Research Institute, Lucknow 226001, Uttar Pradesh, India.
Sarswat
Amit
A
Lal
Nand
N
Sharma
Vishnu L
VL
Jain
Ashish
A
Kumar
Rajeev
R
Verma
Vikas
V
Maikhuri
Jagdamba P
JP
Kumar
Awanit
A
Shukla
Praveen K
PK
Gupta
Gopal
G
D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D005658:Fungi / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D008826:Microbial Sensitivity Tests; D013094:Spermatozoa / Q000187:drug effects; D014246:Trichomonas vaginalis / Q000187:drug effects
D000890:Anti-Infective Agents; D007093:Imidazoles; C029899:imidazole