Structural basis for selective inhibition of Cyclooxygenase-1 (COX-1) by diarylisoxazoles mofezolac and 3-(5-chlorofuran-2-yl)-5-methyl-4-phenylisoxazole (P6)

Cingolani, G.; Panella, A.; Perrone, M. G.; Vitale, Paola; Di Mauro, G.; Fortuna, C. G.; Armen, R. S.; Ferorelli, S.; Scilimati, Smith W. L.; A,

doi:10.1016/j.ejmech.2017.06.045

The diarylisoxazole molecular scaffold is found in several NSAIDs, especially those with high selectivity for COX-1. Here, we have determined the structural basis for COX-1 binding to two diarylisoxazoles: mofezolac, which is polar and ionizable, and 3-(5-chlorofuran-2-yl)-5-methyl-4-phenylisoxazole (P6) that has very low polarity. X-ray analysis of the crystal structures of COX-1 bound to mofezolac and 3-(5-chlorofuran-2-yl)-5-methyl-4-phenylisoxazole allowed the identification of specific binding determinants within the enzyme active site, relevant to generate structure/activity relationships for diarylisoxazole NSAIDs

Titolo:	Structural basis for selective inhibition of Cyclooxygenase-1 (COX-1) by diarylisoxazoles mofezolac and 3-(5-chlorofuran-2-yl)-5-methyl-4-phenylisoxazole (P6)
Autori interni:	Cingolani G. Panella A. Perrone M. G. Vitale Paola DI MAURO, GIUSEPPE [Membro del Collaboration Group] FORTUNA, COSIMO GIANLUCA [Membro del Collaboration Group] Armen R. S. Ferorelli S. Smith W. L. Scilimati A mostra contributor esterni nascondi contributor esterni
Data di pubblicazione:	2017
Rivista:	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Handle:	http://hdl.handle.net/20.500.11769/321530
Appare nelle tipologie:	1.1 Articolo in rivista

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http://hdl.handle.net/20.500.11769/321530

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