The molecular basis for coxib inhibition of p38alpha MAP kinase |
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| Authors: | Sperandio da Silva Gilberto M Lima Lidia M Fraga Carlos A M Sant'Anna Carlos M R Barreiro Eliezer J |
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| Institution: | 1. Department of Chemistry & Physics, College of Arts & Sciences, Florida Gulf Coast University, 10501 FGCU Blvd. S., Fort Myers, FL 33965, USA;2. Pennsylvania State University at Mont Alto, 1 Campus Drive, Mont Alto, PA 17237, USA;3. Department of Bioengineering and Software Engineering, U.A. Whitaker College of Engineering, Florida Gulf Coast University, 10501 FGCU Blvd. S., Fort Myers, FL 33965, USA;4. Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM 87131, USA;1. Key Laboratory of Biology and Genetic Resources of Tropical Crops, Ministry of Agriculture, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China;2. College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, China;1. Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Diseases (MIND), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129-2060, USA;2. Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen 9747 AG, The Netherlands;3. Alzheimer Research Unit, MassGeneral Institute for Neurodegenerative Diseases (MIND), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129-2060, USA;4. Department of Neurology, Qingdao Municipal Hospital, Qingdao University, PR China;5. Department of Neurosciences, University of California, La Jolla, San Diego, CA 92093-0624, USA;6. Research Biologist, VA San Diego Healthcare System, La Jolla, CA, 92161, United States |
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| Abstract: | In this work, we present the results of two combined approaches, molecular docking and comparative molecular field analysis (CoMFA), to propose how the selective cyclooxygenase-2 inhibitor celecoxib could act as a p38 mitogen-activated protein (MAP) kinase inhibitor. The docking analysis revealed why celecoxib has a less favorable binding energy (DeltaG= -12.4kcal/mol) than the selective p38 MAP kinase (p38 MAPK) inhibitor, SB203580 (DeltaG= -22.2kcal/mol). The CoMFA results revealed unfavorable steric effects that can be related to the predicted lower p38 MAP kinase inhibitory activity of celecoxib. Additionally, FlexX and CoMFA results also suggested that etoricoxib, another selective COX-2 inhibitor, could inhibit p38 MAP kinase. |
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