Arylidene analogues as selective COX-2 inhibitors: synthesis, characterization, in silico and in vitro studies

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, ¹H NMR, ¹³C 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

Communicated by Ramaswamy H. Sarma

Keywords:

• Arylidine
• pyrazole
• COX-2 enzymes
• anti-inflammatory
• anti-proliferative

Acknowledgements

Dipti L. Namera is thankful to FIST-DST and SAP-UGC for instrumentation support and MSME Foundation for financial support as a project fellow for ‘Facility for Preservation of Molecular Diversity’ (FPMD) project. Special thanks to ‘National Facility for Drug Discovery through New Chemical Entities (NSE) Development & Instrumentation Support to Small Manufacturing Pharma Enterprises’ Programme under and Pharma Research Support (DPRS) jointly funded by Department of Science & Technology, New Delhi, Government of Gujarat Industries Commissionerate & Saurashtra University, Rajkot.

Disclosure statement

The authors declare that they have no conflict of interest.