Design and synthesis of neoteric benzylidene amino-benzimidazole scaffolds for antioxidant and anti-inflammatory activity

Aim: To design a series of neoteric benzylidene amino-benzimidazole derivatives and to synthesize and evaluate them for anti-inflammatory and antioxidant potential. Methods: The designed target scaffolds were synthesized and appraised for in vitro antioxidant action and in vivo anti-inflammatory potential. AutoDock Vina software was employed for design; the Mannich reaction was used for synthesis; and antioxidant and anti-inflammatory potential were demonstrated by the 2,2-diphenyl-1-picryl hydrazyl free-radical scavenging assay and carrageenan-induced paw edema method, respectively. Results: Methyl-incorporating molecules 3-(2-((2-methylbenzylidene)amino)-1H-benzo[d]imidazol-1-yl)-1-phenylpropan-1-one (6c) and 3-(2-((4-methylbenzylidene)amino-1H-benzo[d]imidazol-1-yl)-1-phenylpropan-1-one (6j) showed remarkable antioxidant and anti-inflammatory action, followed by compounds 6f, 6e and 6i containing 3-CH3, 2-OH, 4-F substituents, respectively. Conclusion: The designed analogs were dynamically confined within the active site of cyclooxygenase-2, and in vitro and in vivo results agreed with molecular docking studies.

Automated summary

The aim of this study was to design and synthesize a series of neoteric benzylidene amino-benzimidazole derivatives and evaluate their anti-inflammatory and antioxidant potential. The designed target scaffolds were synthesized and assessed for their in vitro antioxidant activity and in vivo anti-inflammatory potential. Results showed that compounds 6c and 6j exhibited remarkable antioxidant and anti-inflammatory effects, followed by compounds 6f, 6e, and 6i. Molecular docking studies supported the in vitro and in vivo findings.