Modification of the lead molecule: Tryptophan and piperidine appended triazines reversing inflammation and hyeperalgesia in rats |
| |
| Institution: | 1. Department of Chemistry, Centre for Advanced Studies, Guru Nanak Dev University, Amritsar 143005, India;2. Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143005, India;1. Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1–3, Moscow 119991, Russian Federation;2. EDASA Scientific, Via Stingi 37, San Salvo 66050, Italy;3. Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan;4. Dulbecco Telethon Laboratory of Prions & Amyloids, Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, Trento 38123, Italy;5. A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilov St. 28, Moscow, Russian Federation;1. La Trobe Institute for Molecular Science, La Trobe University, Victoria 3086, Australia;2. School of Science, University of New South Wales, Canberra 2610, Australia;3. School of Chemistry, University of Wollongong, Wollongong, NSW 2522, Australia;4. Walter and Eliza Hall Institute, Parkville, Victoria 3052, Australia;5. Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia;1. Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Cambridge, MA 02139, United States;2. Cardiovascular and Metabolic Diseases, Novartis Institutes for BioMedical Research, Cambridge, MA 02139, United States;3. PK Sciences, Novartis Institutes for BioMedical Research, Cambridge, MA 02139, United States;1. Department of Pharmacy and Pharmaceutical Sciences, “A. Moro” University of Bari, Bari, Italy;2. Department of Pharmacy, “G. d''Annunzio” University of Chieti-Pescara, Chieti, Italy;3. Section In Silico Biology & Machine Learning, Leibniz-Institute for Food Systems Biology at the Technical University of Munich, Freising, Germany |
| |
| Abstract: | The structural optimization of the molecules making them to fit into the active site pocket of COX-2 occupying the same space as covered by the natural substrate arachidonic acid helped in the emergence of compound 10 as an efficacious anti-inflammatory agent. Selective for COX-2 over COX-1, compound 10 exhibited IC50 0.02 µM for COX-2 and reversed acetic acid induced inflammation in rats by 73% when used at 10 mg kg?1 dose and the same dose of the compound also rescued the animals from inflammatory phase of formalin induced hyperalgesia. As evidenced by the results of molecular modeling studies supported by the nuclear Overhauser enhancement data, the appropriate geometry of the molecule in the active site pocket of COX-2 contributing to its H-bond/hydrophobic interactions with Ser530, Trp387 and Tyr385 seems responsible for the enzyme inhibitory activity of the compound. |
| |
| Keywords: | Triazine-tryptophan hybrids Anti-inflammatory Cyclooxygenase-2 Molecular modeling |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
