Aim: The objective of this study was to synthesize and validate a set of compounds that selectively inhibit mPGES-1, with the potential to be developed into a novel anti-inflammatory drug. Methods: The synthesized compounds were characterized using 1H NMR spectroscopy and LC-MS to confirm their structure. Cellular and enzymatic assays were used to demonstrate their inhibitory activity on prostaglandin E2 production. Results: Docking studies revealed that compounds containing fluoro-, chloro- and methyl- groups displayed strong inhibitory activity against prostaglandin E2. The inhibitory activity of synthesized trimethyl and trifluoro was further validated using enzymatic and cell migration assays. Conclusion: The findings demonstrated that the synthesized compounds possess significant potential as a new generation of nonsteroidal anti-inflammatory drugs that selectively target mPGES-1 with fewer side effects.
Keywords: COX-2; COX-2-10aa-PGIS; COX-2-10aa-mPGES-1; anti-inflammation; enzymelink; mPGES-1 inhibitor; microsomal prostaglandin E2 synthase-1; prostacyclin.