Design,synthesis, anti-inflammatory activity and molecular docking of potential novel antipyrine and pyrazolone analogs as cyclooxygenase enzyme (COX) inhibitors |
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| Authors: | Mardia T El Sayed Marwa AMSh El-Sharief Eman S Zarie Nesrin M Morsy Ahmed R Elsheakh Andrey Voronkov Vladimir Berishvili Ghada S Hassan |
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| Institution: | 1. Deparment of Applied Organic Chemistry, National Research Centre, 12622 Dokki, Egypt;2. Department of Chemotherapy, National Research Centre, 12622 Dokki, Egypt;3. Material Science Department, Aalto University, Kemistintie 1, 00076 Aalto, Finland;4. Deparment of Organometallic and Organometalloid Chemistry, National Research Centre, 12622 Dokki, Egypt;5. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt;6. Digital Bio Pharm Ltd., 145-157 St. John Street, London EC1V 4PW, UK;g. Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt;h. Department of Chemistry, Lomonosov Moscow State University, 1/3, Moscow 119991, Russia |
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| Abstract: | As a part of a directed program for development of new active agents, novel heterocyclic derivatives with antipyrine and pyrazolone moieties -incorporated in- have been designed and synthesized. Starting with 4-arylidene-3-methyl-1-phenyl-5-pyrazolone derivative 2a,b novel Mannich bases derivatives have been synthesized and biologically evaluated for their anti-inflammatory activity. Furthermore, the activity of such compounds has been tested interestingly as COX-1 and COX-2 inhibitors. Structure elucidation of the synthesized compounds was attained by the use of elemental analysis, IR, 1H NMR, 13C NMR, and Mass spectrometry techniques. Compounds 3b, 3d and 4b represent the high % inhibition values for both COX-1 and COX-2. On the other hand, compound 8 showed little selectivity against COX-2 while compound 10 showed good selectivity against COX-1 only. Structure activity relationship has been discussed and the results were confirmed by molecular docking calculations. |
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| Keywords: | Synthesis Antipyrine Pyrazolone derivatives COX-1 COX-2 Anti-inflammatory activity Molecular modeling |
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