Open Access. Powered by Scholars. Published by Universities.®
- Discipline
Articles 1 - 2 of 2
Full-Text Articles in Medical Biochemistry
Structural Basis For Selective Inhibition Of Cyclooxygenase-1 (Cox-1) By Diarylisoxazoles Mofezolac And 3-(5-Chlorofuran-2-Yl)-5-Methyl-4-Phenylisoxazole (P6)., Gino Cingolani, Andrea Panella, Maria Grazia Perrone, Paola Vitale, Giuseppe Di Mauro, Cosimo G G. Fortuna, Roger S. Armen, Savina Ferorelli, William L. Smith, Antonio Scilimati
Structural Basis For Selective Inhibition Of Cyclooxygenase-1 (Cox-1) By Diarylisoxazoles Mofezolac And 3-(5-Chlorofuran-2-Yl)-5-Methyl-4-Phenylisoxazole (P6)., Gino Cingolani, Andrea Panella, Maria Grazia Perrone, Paola Vitale, Giuseppe Di Mauro, Cosimo G G. Fortuna, Roger S. Armen, Savina Ferorelli, William L. Smith, Antonio Scilimati
Department of Biochemistry and Molecular Biology Faculty Papers
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.
Mc-Ppea As A New And More Potent Inhibitor Of Clp-Induced Sepsis And Pulmonary Inflammation Than Fk866., Peixin Huang, Mark W Lee, Keivan Sadrerafi, Daniel P. Heruth, Li Q. Zhang, Dev Maulik, Shui Qing Ye
Mc-Ppea As A New And More Potent Inhibitor Of Clp-Induced Sepsis And Pulmonary Inflammation Than Fk866., Peixin Huang, Mark W Lee, Keivan Sadrerafi, Daniel P. Heruth, Li Q. Zhang, Dev Maulik, Shui Qing Ye
Manuscripts, Articles, Book Chapters and Other Papers
Our previous study indicated that overexpression of nicotinamide phosphoribosyltransferase (NAMPT) aggravated acute lung injury, while knockdown of NAMPT expression attenuated ventilator-induced lung injury. Recently, we found that meta-carborane-butyl-3-(3-pyridinyl)-2E-propenamide (MC-PPEA, MC4), in which the benzoylpiperidine moiety of FK866 has been replaced by a carborane, displayed a 100-fold increase in NAMPT inhibition over FK866. Here, we determined the effects of MC4 and FK866 on cecal ligation and puncture (CLP) surgery-induced sepsis in C57BL/6J mice. MC4 showed stronger inhibitory effects than FK866 on CLP-induced mortality, serum tumor necrosis factor α (TNFα) levels, pulmonary myeloperoxidase activity, alveolar injury, and interleukin 6 and interleukin1β messenger …