Agents targeting microsomal prostaglandin E-2 synthase-1 (mPGES-1) would inhibit only PGE(2) production induced by inflammatory stimuli and thus could represent a valuable alternative to non-steroidal anti-inflammatory drugs (NSAIDs) as they should be free from the severe side effects of the classic anti-inflammatory drugs. Although several mPGES-1 inhibitors have been so far identified, none of them is currently in clinical trials, therefore the discovery of new molecular platforms, able to interfere with this interesting target, is urgently required. Here, we report the results of a focused collection of dyhidropyrimidin-2(1H)-one based molecules projected by Virtual Screening computational techniques. The key interactions with the receptor counterpart were introduced as a qualitative filter for the selection of the most promising compounds. The biological data obtained are consistent with the computer-aided suggestions and disclosed two interesting molecules showing in vitro mPGES-1 inhibitory activity in the low mu M range.

Exploration of the dihydropyrimidine scaffold for the development of new potential anti-inflammatory agents blocking prostaglandin E2 synthase-1 enzyme (mPGES-1)

LAURO, GIANLUIGI;STROCCHIA, MARIA;TERRACCIANO, Stefania;BRUNO, Ines;RICCIO, Raffaele;BIFULCO, Giuseppe
2014

Abstract

Agents targeting microsomal prostaglandin E-2 synthase-1 (mPGES-1) would inhibit only PGE(2) production induced by inflammatory stimuli and thus could represent a valuable alternative to non-steroidal anti-inflammatory drugs (NSAIDs) as they should be free from the severe side effects of the classic anti-inflammatory drugs. Although several mPGES-1 inhibitors have been so far identified, none of them is currently in clinical trials, therefore the discovery of new molecular platforms, able to interfere with this interesting target, is urgently required. Here, we report the results of a focused collection of dyhidropyrimidin-2(1H)-one based molecules projected by Virtual Screening computational techniques. The key interactions with the receptor counterpart were introduced as a qualitative filter for the selection of the most promising compounds. The biological data obtained are consistent with the computer-aided suggestions and disclosed two interesting molecules showing in vitro mPGES-1 inhibitory activity in the low mu M range.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11386/4504857
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