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Scientia Pharmaceutica is published by MDPI from Volume 84 Issue 3 (2015). Articles in this Issue were published by another publisher in Open Access under a CC-BY (or CC-BY-NC-ND) licence. Articles are hosted by MDPI on as a courtesy and upon agreement with Austrian Pharmaceutical Society (Österreichische Pharmazeutische Gesellschaft, ÖPhG).
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Sci. Pharm. 2015, 83(1), 15-26; (registering DOI)

Design, Synthesis, and Biological Evaluation of New 2-Phenyl-4H-chromen-4-one Derivatives as Selective Cyclooxygenase-2 Inhibitors

Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Author to whom correspondence should be addressed.
Received: 26 July 2014 / Accepted: 15 September 2014 / Published: 15 September 2014
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In order to develop new selective COX-2 inhibitors, a new series of 2-phenyl-4H-chromen-4-one derivatives possessing a methylsulfonyl pharmacophore group at the para position of the C-4 phenyl ring were designed, synthesized, and evaluated for cyclooxygenase-2 inhibitory activity. In vitro COX-1/COX-2 isozyme inhibition structure-activity studies identified 3-(benzyloxy)-2-[4-(methylsulfonyl)phenyl]-4H-chromen-4-one (5d) as a potent COX-2 inhibitor (IC50 = 0.07 μM) with a high COX-2 selectivity index (SI = 287.1) comparable to the reference drug celecoxib (COX-2 IC50 = 0.06 μM; COX-2 SI = 405). A molecular modeling study where 3-(benzyloxy)-2-[4-(methylsulfonyl)phenyl]-4H-chromen-4-one (5d) was docked into the active site of COX-2 showed that the p-MeSO2 substituent on the C-4 phenyl ring was well-oriented in the vicinity of the COX-2 secondary pocket (Arg513, Val523, and His90) and the carbonyl group of the chromene ring could interact with Ser530. The structure-activity data acquired indicated that the nature and size of the substituent on the C-3 chromene scaffold are important for COX-2 inhibitory activity. Our results also indicated that the chromene moiety constitutes a suitable template to design new COX-2 inhibitors.
Keywords: Chromene derivatives; Docking studies; COX-2 inhibitory activity Chromene derivatives; Docking studies; COX-2 inhibitory activity
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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ZARGHI, A.; KAKHKI, S. Design, Synthesis, and Biological Evaluation of New 2-Phenyl-4H-chromen-4-one Derivatives as Selective Cyclooxygenase-2 Inhibitors. Sci. Pharm. 2015, 83, 15-26.

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