Benzodioxole –Pyrazole Hybrids as Anti‐Inflammatory and Analgesic Agents with COX‐1,2/5‐LOX Inhibition and Antioxidant Potential

Two series of benzodioxole–pyrazole hybrids were synthesized and the IC50 values for in vitro inhibition of the enzymes cyclooxygenase 1/2 (COX‐1, COX‐2) and 5‐lipoxygenase (5‐LOX) were investigated. All compounds were tested for their in vivo anti‐inflammatory and analgesic potentials using diclofenac sodium as a reference standard. Compounds 4, 11, 17, 20, 21, 26, and 27, which showed good analgesic and/or anti‐inflammatory activities, were also evaluated for their ability to inhibit tumor necrosis factor (TNF)‐α production, myeloperoxidase and proteinase, beside their antioxidant activity. Collectively, compounds 11, 17, and 26 displayed significant anti‐inflammatory, analgesic, and antioxidant activities, beside dual COX‐2 and 5‐LOX inhibition. Among these, compound 26 showed high selectivity for in vitro COX‐1/COX‐2 inhibition, whereas the analogs 11 and 17 noticeably ameliorated the TNF‐α level by 85.19 and 97.71%, respectively. A molecular docking study was performed to investigate the possible binding mode of compounds 11, 17, and 26 with the active sites of the COX‐2 and 5‐LOX enzymes, where they showed nearly the same binding pattern as that of celecoxib and meclofenamic acid, respectively. In two series of benzodioxole–pyrazole hybrids, compounds 11, 17, and 26 displayed significant anti‐inflammatory, analgesic and antioxidant activities, beside dual cyclooxygenase‐2 (COX‐2) and 5‐lipoxygenase (5‐LOX) inhibition. Compo...
Source: Archiv der Pharmazie - Category: Drugs & Pharmacology Authors: Tags: Full Paper Source Type: research