Design, synthesis, biological assessment and in silico ADME prediction of new 2-(4-(methylsulfonyl) phenyl) benzimidazoles as selective cyclooxygenase-2 inhibitors

Mohamed A S Badawy; Eman K A Abdelall; El-Shaymaa El-Nahass; Khaled R A Abdellatif; Hamdy M Abdel-Rahman

doi:10.1039/d1ra04756f

Design, synthesis, biological assessment and in silico ADME prediction of new 2-(4-(methylsulfonyl) phenyl) benzimidazoles as selective cyclooxygenase-2 inhibitors

RSC Adv. 2021 Aug 17;11(44):27659-27673. doi: 10.1039/d1ra04756f. eCollection 2021 Aug 9.

Authors

Mohamed A S Badawy¹, Eman K A Abdelall², El-Shaymaa El-Nahass³, Khaled R A Abdellatif^{2

4}, Hamdy M Abdel-Rahman^{1

5}

Affiliations

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Nahda University (NUB) Beni-Suef 62513 Egypt Mohamed.aboalhassan@nub.edu.eg +2001066394559.
² Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University Beni-Suef 62514 Egypt.
³ Department of Pathology, Faculty of Veterinary Medicine, Beni-Suef University Beni-Suef 62511 Egypt.
⁴ Pharmaceutical Sciences Department, IbnSina National College for Medical Studies Jeddah Kingdom of Saudi Arabia.
⁵ Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University Assiut 71526 Egypt.

Abstract

A novel series of benzimidazole derivatives wherein 4-(methylsulfonyl) phenyl pharmacophore attached via its C-2 position was designed and synthesized. These compounds were evaluated in vitro as cyclooxygenase-1(COX-1)/cyclooxygenese-2(COX-2) inhibitors. Furthermore, the synthesized compounds were also in vivo evaluated for their anti-inflammatory activity and ulcerogenic liability. Examination of histopathological lesions was also performed to evaluate the cariogenic effect of most active compounds. In silico prediction of physicochemical properties, ADME, and drug-likeness profiles were also studied. Several compounds as 11b, 11k, 12b, and 12d showed selective inhibition to (COX-2) isozyme. Compound 11b showed the most potent (COX-2) inhibitory activity with (IC₅₀ = 0.10 μM) and selectivity index (SI = 134); the tested compounds also have shown good anti-inflammatory activity. Regarding the ulcerogenic liability, compound 11b was also safest one (Ulcer Index) (UI = 0.83). The results of the molecular docking studies is closely related to the results of the in vitro COX-2 inhibitory activities.