Novel quinoline incorporating 1,2,4-triazole/oxime hybrids: Synthesis,molecular docking,anti-inflammatory,COX inhibition,ulceroginicity and histopathological investigations |
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| Institution: | 1. Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt;2. Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, TX 78712, USA;1. H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University Karachi, Karachi 75270, Pakistan;2. Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia;3. PCSIR Laboratories Complex, Karachi, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi 75280, Pakistan;4. Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21412, Saudi Arabia;1. Department of Chemistry, National College, Tiruchirappalli, 620 001, India;2. R&D Center, Orchid Pharma Ltd., Chennai, 600119, India;3. Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai, 600025, India;4. Department of Bioinformatics, Biomolecular Crystallography Laboratory, School of Chemical and Biotechnology, SASTRA University, Thanjavur, 613 401, India;5. Department of Chemistry, North Eastern Hill University, Shillong, 793022, Meghalaya, India;1. Advanced Organic Chemistry Department, P.D. Patel Institute of Applied Sciences, CHARUSAT, Changa 388421, Gujarat, India;2. P.G. Department of Biosciences, Sardar Patel University, Vallabh Vidyanagar 388120, Gujarat, India;3. Madhav University, Abu Road, Sirohi 307026, Rajasthan, India;1. Medicinal Chemistry Department, Faculty of Pharmacy, Minia University, Minia 61519, Egypt;2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, 06100 Sihhiye, Ankara, Turkey;1. Karadeniz Technical University, Department of Chemistry 61080 Trabzon, Turkey;2. Recep Tayyip Erdogan University, Department of Chemistry, 53100 Rize, Turkey;3. Dept. of Biotechnology, School of Bio-Sciences and Technology, VIT, Vellore 632014, India;1. Institute of New Drug Development, China Medical University, No. 91 Hsueh-Shih Rd., Taichung 40402, Taiwan;2. Ph.D. Program for Biotech Pharmaceutical Industry, China Medical University, No. 91, Hsueh-Shih Rd., Taichung 40402, Taiwan;3. School of Pharmacy, China Medical University, No. 91, Hsueh-Shih Rd., Taichung 40402, Taiwan;4. Master Program for Pharmaceutical Manufacture, China Medical University, No. 91, Hsueh-Shih Rd., Taichung 40402, Taiwan;5. Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, No. 91, Hsueh-Shih Rd., Taichung 40402, Taiwan;6. Department of Food Nutrition and Health Biotechnology, Asia University, Taichung 41354, Taiwan;7. Division of Metabolism, Department of Internal Medicine, China Medical University, Taichung 40402, Taiwan |
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| Abstract: | A series of novel quinolines incorporating 1,2,4-triazole/oxime hybrids were prepared. They showed remarkable anti-inflammatory activity and exhibited very low incidence of gastric ulceration, compared to indomethacin. Most of the compounds tested showed remarkable inhibition of the COX-1 isozyme, with IC50’s ranging from 0.48 to 28 µM. Compounds 7c and 9g showed high safety profiles with normal stomach tissue integrity. Docking studies supported the observed in vitro inhibitory activity towards the COX enzymes that may explain their promising anti-inflammatory activity relative to indomethacin. Moreover, differences between the COX-1 and COX-2 isozymes in observed energy scores, as well as in the number of interactions with some of the compounds tested, might predict their higher selectivity towards COX-1 rather than COX-2. Compound 9e was found to inhibit both COXs non-competitively with Ki values of 81 µM and 94.6 µM. |
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| Keywords: | Quinoline Oxime Anti-inflammatory COX inhibition Ulceroginicity Histopathology |
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