Analgesic, anti-inflammatory, and antimicrobial activities of novel isoxazole/pyrimidine/pyrazole substituted benzimidazole analogs

Abstract

From o-phenylenediamine and p-amino benzoic acid, several new 3-methylisoxazol-5(4H)-one/2-hydroxy/mercapto-6-methylpyrimidin-4(5H)-one/3-methyl-1-substituted-1H-pyrazol-5(4H)-one substituted benzimidazole derivatives 5–16 were synthesized through multi step synthesis based on hybrid approach. All test compounds were screened for its analgesic, anti-inflammatory, and in vitro antimicrobial activity by tail flick method, carrageenan induced foot paw edema method and agar streak dilution method, respectively. Most active compounds were examined for its ulcerogenicity by pylorus ligation method. The relationship between chemical structure and biological activities of the test compounds were discussed. Among various tested compounds, 4-(2-(4-(1H-benzimidazol-2-yl)phenyl)hydrazono)-1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5(4H)-one 10 was found to be most potent compound. This compound showed 72% analgesic activity (20 mg/kg; second hour) and 67% protection in paw edema test (20 mg/kg; second hour) which are comparable with that of standard Diclofenac [69% analgesic activity (20 mg/kg; second hour) and 65% protection in paw edema test (20 mg/kg; second hour)]. In addition, compound 10 exhibited least ulcer index which is about 1/3 of the ulcer index of reference standard and showed good antibacterial and moderate antifungal activity.