Title:Synthesis and Pharmacological Evaluation of Tetrazolobenzimidazoles as Novel Anti-inflammatory Agents
VOLUME: 15 ISSUE: 2
Author(s):Mayura A. Kale, Rajesh B. Nawale, Manjiri R. Peharkar and Sharad V. Kuberkar
Affiliation:Government College of Pharmacy, Opposite Government Polytechnic, Railway station road, Osmanpura, Aurangabad (M.S), India - 431 005.
Keywords:2-Mercaptobenzimidazole, anti-inflammatory activity, tetrazole, ulcer index.
Abstract:Background: Currently used anti-inflammatory drugs are associated with some
severe side effects such as gastric irritation, which may range from simple discomfort to ulcer
formation. Therefore, the development of potent anti-inflammatory drugs with fewer side
effects is important. Benzimidazole, tetrazole and its various derivatives have been used in
the synthesis of numerous heterocyclic compounds. In the past few decades, these compounds
received much attention due to their diverse array of biological activities. As these
heterocycles are known to possess anti-inflammatory activity individually, we thought it
worthwhile to link these heterocycles, synthesize them and evaluate for possible changes in
this anti-inflammatory activity.
Methods: Novel benzimidazole linked tetrazole compound 2-{[2-(1H-tetrazole-5-yl)ethyl]
sulfanyl}-1,3-benzimidazole (3) was synthesized by cyclization of 3-(1,3-benzimidazol-2-ylsulfanyl)
propanenitrile in presence of sodium azide. A series of tetrazolobenzimidazole
derivatives (3a-h) were synthesized by the reaction of compound (3) with acid chlorides. All
the synthesized compounds were subjected to structural elucidation by IR,
1H-NMR spectroscopy,
Mass spectrometry and elemental analyses. The newly synthesized compounds were
screened for anti-inflammatory activity by carrageenan-induced paw oedema method in albino
rats.
Results: Compounds (3a, 3c, 3g) which contain acetyl, benzoyl and benzoyl moieties;
respectively at N-1of tetrazole exhibited anti-inflammatory activities comparable with
standard drug diclofenac. Other compounds exhibited anti-inflammatory activity less than the
standard. The differences between control and treatment group were tested using one way
ANOVA followed by Dunnett’s test. A probability value less than 0.01 was considered to be
statistically significant. The GraphPad Instat 3.0 version was used for statistical analysis.
Conclusion: Synthesized compounds having anti-inflammatory activity better than standard
were found to be 1-{5-[2-(benzimidazol-2-yl-sulfanyl)ethyl]-2H-tetrazol-2yl}methanone (3c)
and 1-{5-[5-methoxy-2-(benzimidazol-2-yl-sulfanyl)ethyl]-2H-tetrazol-2yl}methanone (3g)
and the compounds (3a, 3e, 3f) were found to exhibit anti-inflammatory activity comparable
to that of standard. All the compounds were found to cause less gastric ulceration than the
standard drug diclofenac.
