Synthesis,biological evaluation and docking study of N-(2-(3,4,5-trimethoxybenzyl)benzoxazole-5-yl) benzamide derivatives as selective COX-2 inhibitor and anti-inflammatory agents |
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| Institution: | 1. Department of Pharmaceutical Chemistry, Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), Mehrauli-Badarpur Road, PushpVihar, Sector-3, New Delhi 110017, India;2. Faculty of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak 124001, India;1. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia;2. Department of Chemistry, Faculty of Science and Technology, Al-Neelain University, Khartoum, Sudan;3. Department of Biochemistry, College of Science, King Saud University, PO Box 22452, Riyadh 11451, Saudi Arabia;1. Department of Medicinal Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt;2. Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, Taif 21974, Saudi Arabia;3. Sharjah Institute for Medical Research and College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates;4. Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt;5. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt;1. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt;2. Department of Microbiology and Immunology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt;1. Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan;2. Faculty of Science and Engineering, Setsunan University, 17-8 Ikedanaka-machi, Neyagawa, Osaka 573-8508, Japan;3. Graduate School of Medicine, Kyoto University, 53 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan;4. Research and Development Group for In Silico Drug Discovery, Center for Cluster Development and Coordination (CCD), Foundation for Biomedical Research and Innovation at Kobe (FBRI), 6-3-5, Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan;5. Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan;1. Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt;2. Pharmacology Department, Faculty of Veterinary, Cairo University, Cairo, Egypt;1. Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut 71526, Assiut, Egypt;2. Pharmaceutical Chemistry Department, College of Pharmacy, Jouf University, Sakaka, Aljouf 2014, Saudi Arabia;3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, 82524 Sohag, Egypt;4. Department of Chemistry, Faculty of Science, Sohag University, Sohag 82524, Egypt;5. Pharmacology Department, College of Pharmacy, Jouf University, Sakaka, Aljouf 2014, Saudi Arabia;6. Biochemistry Department, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt |
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| Abstract: | A series of N-(2-(3,4,5-trimethoxybenzyl)-benzoxazole-5-yl)benzamide derivatives (3a–3n) was synthesized and evaluated for its in vitro inhibitory activity against COX-1 and COX-2. The compounds with considerable in vitro activity (IC50 < 1 µM), were evaluated in vivo for their anti-inflammatory and ulcerogenic potential. Out of the fourteen newly synthesized compounds; 3b, 3d, 3e, 3h, 3l and 3m were found to be most potent COX-2 inhibitors in in vitro enzymatic assay with IC50 in the range of 0.14–0.69 µM. In vivo anti-inflammatory activity of these six compounds (3b, 3d, 3e, 3h, 3l and 3m) was assessed by carrageenan induced rat paw edema method. The compound 3b (79.54%), 3l (75.00%), 3m (72.72%) and 3d (68.18%) exhibited significant anti-inflammatory activity than standard drug ibuprofen (65.90%). Ulcerogenic activity with histopathological studies was performed, and the screened compounds demonstrated significant gastric tolerance than ibuprofen. Molecular Docking study was also performed with resolved crystal structure of COX-2 to understand the interacting mechanisms of newly synthesized inhibitors with the active site of COX-2 enzyme and the results were found to be in line with the biological evaluation studies of the compounds. |
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| Keywords: | COX-1 COX-2 Anti-inflammatory activity Ulcerogenic activity Histopathology |
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