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Discovery of 3-hydroxy-3-pyrrolin-2-one-based mPGES-1 inhibitors using a multi-step virtual screening protocol

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Abstract

Targeting microsomal prostaglandin E2 synthase-1 (mPGES-1) represents an efficient strategy for the development of novel drugs against inflammation and cancer with potentially reduced side effects. With this aim, a virtual screening was performed on a large library of commercially available molecules using the X-ray structure of mPGES-1 co-complexed with a potent inhibitor. Combining fast ligand-based shape alignment, molecular docking experiments, and qualitative analysis of the binding poses, a small set of molecules was selected for the subsequent steps of validation of the biological activity. Compounds 2 and 3, bearing the 3-hydroxy-3-pyrrolin-2-one nucleus, showed mPGES-1-inhibitory activity in the low micromolar range. These data highlighted the applicability of the reported virtual screening protocol for the selection of new mPGES-1 inhibitors as promising anti-inflammatory/anti-cancer drugs.

Graphical abstract: Discovery of 3-hydroxy-3-pyrrolin-2-one-based mPGES-1 inhibitors using a multi-step virtual screening protocol

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Publication details

The article was received on 02 Oct 2018, accepted on 17 Nov 2018 and first published on 20 Nov 2018


Article type: Research Article
DOI: 10.1039/C8MD00497H
Citation: Med. Chem. Commun., 2018, Advance Article
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    Discovery of 3-hydroxy-3-pyrrolin-2-one-based mPGES-1 inhibitors using a multi-step virtual screening protocol

    G. Lauro, V. Cantone, M. Potenza, K. Fischer, A. Koeberle, O. Werz, R. Riccio and G. Bifulco, Med. Chem. Commun., 2018, Advance Article , DOI: 10.1039/C8MD00497H

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