Arylidene analogues as selective COX-2 inhibitors: synthesis, characterization, in silico and in vitro studies. Issue 18 (12th December 2021)

• Record Type: Journal Article
• Authors: Namera, Dipti L.; Thakkar, Sampark S.; Thakor, Parth; Bhoya, Umed; Shah, Anamik
• Is Part Of: Journal of biomolecular structure & dynamics. Volume 39:Issue 18(2021)
• Page Start: 7150
• Page End: 7159
• Publication Date: 2021-12-12
• Subjects: Arylidine -- pyrazole -- COX-2 enzymes -- anti-inflammatory -- anti-proliferative; Biomolecules -- Periodicals; Molecular structure -- Periodicals; Molecular Biology -- Periodicals; Biomechanics -- Periodicals; 572
• DOI: 10.1080/07391102.2020.1806109
• Languages: English
• ISSNs: 0739-1102

Abstract

Abstract: Pyrazole derivatives are known to be as non-steroidal anti-inflammatory drugs (NSAID). Celecoxib is the pioneer sulfonamide being pyrazole derivative COX-2 inhibitors, which used to treat pain and inflammation; they may also have a role in cancer prevention. In the present investigation, a series of arylidene analogues (NDP-4011 to NDP-4016 ) were synthesized by the condensation of 4-(3-methyl-5-oxo-4, 5-dihydro-1H-pyrazol-1-yl) benzenesulfonamide (I ) with various substituted aromatic aldehydes in ethanol using a catalytic amount of piperidine. All the synthesized compounds were well characterized by IR, 1 H NMR, 13 C NMR and mass spectrometry. The cytotoxicity of synthesized compounds was tested on the NRK-52E cell line. From which NDP-4011, NDP-4012, NDP-4013, NDP-1015 and NDP-4016 were found to have higher cytotoxicity whereas NDP-4014 showed less cytotoxicity compared to Celecoxib . The in silico pharmacokinetic parameters of compounds were evaluated to check their candidature as a drug. Molecular docking was carried out on COX-2 structures, which revealed that NDP-4011 to NDP-4016 targets allosteric binding site similar to the binding mode of the selective COX inhibitor Celecoxib . Furthermore, results of in vitro COX-2 inhibition assay supports arylidene analogues as COX-2 inhibitors. GRAPHICAL ABSTRACT: UF0001 Communicated by Ramaswamy H. Sarma