Synthesis and Evaluation of Analgesic and Antioxidant Activities of Substituted Benzimidazole Derivatives

Abstract

The present study describes the synthesis and pharmacological evaluation of a number of substituted benzimidazole derivatives designated by 3A-1, 3A-2, 3A-3, 3B-1 and 3B-2 through condensation of different o-aryldiamine compounds with the corresponding aldehyde employing ammonium salt as a catalyst. All the compounds were characterized by IR and 1H NMR spectroscopic analysis. The synthesized benzimidazole derivatives were investigated for analgesic and antioxidant activities using acetic acid-induced writhing inhibition in Swiss albino mice and DPPH free radical scavenging assay, respectively. Compounds 3A-3, 3B-1 and 3B-2 at a dose of 50 mg/kg body weight reduced the number of writhings by 88.24%, 84.03% and 85.71%, respectively (p<0.001) in comparison with standard diclofenac (90.76% inhibition). The derivatives 3A-1, 3A-2, 3A-3 and 3B-2 showed prominent antioxidant activity with IC50 values of 0.038, 0.959, 8.834 and 7.519 μg/ml, respectively in comparison with the standard butylated hydroxytoluene (BHT) (14.44 μg/ml). Among the synthesized compounds, 3A-3 and 3B- 2 emerged as the most promising analgesic and antioxidant agents and expressed their potential as lead compounds in future research.
 Dhaka Univ. J. Pharm. Sci. 19(1): 37-46, 2020 (June)

Pharmacological Screening of Substituted Benzimidazole Derivatives

“…16 We have also reported the peripheral analgesic and antioxidant activities of some different benzimidazole derivatives with their synthetic pathway. 17 In continuation of our ongoing research work on benzimidazoles [16][17][18] , our present study aims at the evaluation of central analgesic, anti-inflammatory, cytotoxicity, antimicrobial and antioxidant activities of some 2-substituted benzimidazole derivatives with different substituents in various positions of the benzimidazole ring.…”

A Comprehensive Account on Recent Progress in Pharmacological Activities of Benzimidazole Derivatives

“…In contrast, the derivatives containing the 5-sulfonic acid group showed poor or no antioxidant properties. Unsubstituted 2-aromatic ring or OH, IC 50 values than the standard BHT (8.834, 7.519, 0.038 and 0.959 μg/ml, respectively vs. 14.44 μg/ml) (Brishty et al, 2020). Finally, compounds 228 and 229 demonstrated mild antioxidant potential in comparison with standard ascorbic acid (IC 50 12.25 × 10 3 and 87.326 × 10 3 μg/ml, respectively vs. 2.19 μg/ml) (Saha et al, 2021).…”

“…By applying Mannich reaction, Sethi et al (Sethi et al, 2017) prepared a series of N-benzimidazol-1-yl methyl-benzamide derivatives (155-159), having electron-withdrawing groups chloro and bromo at ortho position of phenyl ring (156-158) and chloromethyl group at 2-position of benzimidazole nucleus (155), asserted significant analgesic and anti-inflammatory Recently, Sethi et al (Sethi et al, 2018) synthesized two series of benzimidazole based compounds from the coupling of coumarin and benzimidazole nuclei and narrated the antiinflammatory activity of compounds 164-165 compared to the standard indomethacin (45 vs. 48%). Brishty et al (Brishty et al, 2020) synthesized a group of substituted benzimidazole derivatives amongst which compounds 166, 167 and 168 exhibited remarkable analgesic activity by inhibition of acetic acid induced writhing of mice compared to standard diclofenac (88.24, 84.03 and 85.71%, respectively, vs. 90.76%; p < 0.001). In continuation of the research by the group, Saha et al (Saha et al, 2020) prepared a number of disubstituted benzimidazole derivatives.…”

“…Recently, Sethi et al ( Sethi et al, 2018 ) synthesized two series of benzimidazole based compounds from the coupling of coumarin and benzimidazole nuclei and narrated the anti-inflammatory activity of compounds 164–165 compared to the standard indomethacin (45 vs. 48%). Brishty et al ( Brishty et al, 2020 ) synthesized a group of substituted benzimidazole derivatives amongst which compounds 166, 167 and 168 exhibited remarkable analgesic activity by inhibition of acetic acid induced writhing of mice compared to standard diclofenac (88.24, 84.03 and 85.71%, respectively, vs. 90.76%; p < 0.001). In continuation of the research by the group, Saha et al ( Saha et al, 2020 ) prepared a number of disubstituted benzimidazole derivatives.…”

“…Interestingly, compound 225 exhibited more inhibition (%) of DPPH-free radical than the standard antioxidant Trolox (73% ± 2.42 vs. 70% ± 0.35) ( Ramos Rodríguez et al, 2020 ). Furthermore, compounds 166, 168, 226 and 227 displayed prominent antioxidant property with lower IC 50 values than the standard BHT (8.834, 7.519, 0.038 and 0.959 μg/ml, respectively vs. 14.44 μg/ml) ( Brishty et al, 2020 ) . Finally, compounds 228 and 229 demonstrated mild antioxidant potential in comparison with standard ascorbic acid (IC 50 = 12.25 × 10 3 and 87.326 × 10 3 μg/ml, respectively vs. 2.19 μg/ml) ( Saha et al, 2021 ).…”