Document Type
Article
Publication Date
9-29-2017
Abstract
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.
Recommended Citation
Cingolani, Gino; Panella, Andrea; Perrone, Maria Grazia; Vitale, Paola; Di Mauro, Giuseppe; Fortuna, Cosimo G G.; Armen, Roger S.; Ferorelli, Savina; Smith, William L.; and Scilimati, Antonio, "Structural basis for selective inhibition of Cyclooxygenase-1 (COX-1) by diarylisoxazoles mofezolac and 3-(5-chlorofuran-2-yl)-5-methyl-4-phenylisoxazole (P6)." (2017). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 140.
https://jdc.jefferson.edu/bmpfp/140
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
PubMed ID
28710965
Language
English
Comments
This article has been peer reviewed. It is the authors' final version prior to publication in European Journal of Medicinal Chemistry, Volume 138, September 2017, Pages 661-668.
The published version is available at https://doi.org/10.1016/j.ejmech.2017.06.045. Copyright © Elsevier