Issue 26, 2019

Synthesis, in vitro COX-1/COX-2 inhibition testing and molecular docking study of novel 1,4-benzoxazine derivatives

Abstract

The present work deals with an efficient and straightforward synthesis, biological activity and molecular docking study of novel 1,4-benzoxazine derivatives. Dehydrocyclization through consecutive functionalization of the –OH and –NH bonds of 2-aminophenol derivatives with disubstituted alkynes in the presence of [RuCl2(p-cymene)]2 as a catalyst allows synthesis of 1,4-benzoxazine derivatives in a single synthetic step. Inspired by a literature survey of COX-1/COX-2 enzyme inhibition studies we found that the biphenyl type structure is more suitable to inhibit the concentration of COX-/COX-2 enzymes, and to check the viability of this assumption we performed molecular docking as well as an in vitro COX-1/COX-2 inhibition study for the synthesised derivatives. The results of the assay indicated that compounds 3e, 3f, 3r, and 3s exhibited optimal COX-2 inhibition, with IC50 values of 0.57–0.72 μM, and the selectivity index (SI) range of 186.8–242.4, using Celecoxib as a standard drug (IC50 = 0.30 μM; COX-2 SI: >303). Furthermore, the molecular docking study explored the essential binding mode and possible interactions within the binding site of COX-1/COX-2 isoenzymes. This study identified potential compounds, which can be promising leads for their subsequent development as newer anti-inflammatory agents.

Graphical abstract: Synthesis, in vitro COX-1/COX-2 inhibition testing and molecular docking study of novel 1,4-benzoxazine derivatives

Supplementary files

Article information

Article type
Paper
Submitted
08 Feb 2019
Accepted
14 May 2019
First published
17 May 2019

New J. Chem., 2019,43, 10305-10317

Synthesis, in vitro COX-1/COX-2 inhibition testing and molecular docking study of novel 1,4-benzoxazine derivatives

M. M. Shaikh, A. P. Patel, S. P. Patel and K. H. Chikhalia, New J. Chem., 2019, 43, 10305 DOI: 10.1039/C9NJ00684B

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