Synthesis, Molecular Docking, and Anti-inflammatory Activities of Some Novel Benzimidazole Derivatives as Potential Cyclo-oxygenase-2 Inhibitors

Elrayess, Ranza; Elrayess, Ranwa; Ghareb, Nagat

doi:10.21608/ejchem.2023.218909.8165

Synthesis, Molecular Docking, and Anti-inflammatory Activities of Some Novel Benzimidazole Derivatives as Potential Cyclo-oxygenase-2 Inhibitors

Document Type : Original Article

Authors

¹ Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.

² Zoology Department, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt

10.21608/ejchem.2023.218909.8165

Abstract

Due to the association of inflammatory, cancerous, and neurological illnesses with COX-2 overexpression, targeting of this enzyme has become a potent tool for therapeutic research. In the current research, synthesis of novel, straightforward benzimidazole derivatives was described that were selective COX-2 inhibitors and exhibit a striking in vivo anti-inflammatory activity. The most active candidates were five novel molecules 4a, 4b, 5, 6 and 9 showing promising selectivity and in vitro COX-2 inhibition with IC50 of 0.23, 0.27, 0.24, 0.13, and 0.15 µM respectively in comparison with indomethacin IC50 of 0.41 µM. Additionally, using a carrageenan-induced paw edema method, the anti-inflammatory effectiveness of molecules 4a, 4b, 5, 6, and 9 was assessed in vivo. Results revealed that the synthesized compounds had significant inhibitory potency with action like that of the common drug indomethacin. Finally, to comprehend their way of binding, these substances were docked in the crystal structure of the COX-2 enzyme (PDB ID: 4COX). These discoveries may lead to the creation of novel COX-2 inhibitors with enhanced selectivity.

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