Design,synthesis, modeling studies and biological screening of novel pyrazole derivatives as potential analgesic and anti-inflammatory agents |
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| Affiliation: | 1. Cairo University, Faculty of Pharmacy, Pharmaceutical Organic Chemistry Department, Cairo, Egypt;2. October 6 University (O6U), Faculty of Pharmacy, Pharmaceutical Organic Chemistry Department, 6th of October City, Giza, Egypt;3. Al-Azhar University, Faculty of Pharmacy, Organic Chemistry Department (Girls), Cairo, Egypt;4. Misr University for Science and Technology, Faculty of Pharmacy, Organic Chemistry Department, Giza, Egypt;5. Modern University for Technology and Information, Faculty of Pharmacy, Organic Chemistry Department, Cairo, Egypt;1. Department of Chemistry, Mangalore University, Mangalagangothri, 574199, Karnataka, India;2. PURSE Lab, Mangalore University, Mangalagangothri, 574 199, Karnataka, India;1. Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012, Jinan, Shandong, PR China;2. Department of Immunology, Key Laboratory for Experimental, Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection and Immunology, Shandong University School of Medicine, Jinan, 250012, Shandong Province, PR China;3. Department of Hepatic Diseases, Jinan Infectious Disease Hospital, Jingshi Road, 173, 250021, Jinan, Shandong, PR China;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt;2. Pharmacy Program, Pharmacology Stream, Allied Health Department, College of Health Sciences, University of Bahrain, P.O. Box 32038, Bahrain;3. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Kafrelsheikh University, Kafr El-Sheikh, 33516, Egypt;4. Pharmaceutical Chemistry Department, Faculty of Pharmacy, The British University in Egypt, Al-Sherouk City, Cairo, Egypt;5. Department of Biohemistry, Faculty of Science, Alexandria University, Alexandria, Egypt;6. Food Sciences, University of Otago, Dunedin, New Zealand;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, ‘Carol Davila’ University of Medicine and Pharmacy, Traian Vuia 6, Bucharest 020956, Romania;2. C.D. Nenitzescu Institute of Organic Chemistry, 202B Spl. Independentei, Bucharest 060023, Romania;3. Stefan S Nicolau Institute of Virology, 285 Mihai Bravu Avenue, Bucharest 030304, Romania;1. Department of Chemistry, St. Berchmans College (Autonomous), Changanassery, Kerala, India;2. Department of Physics, Fatima Mata National College (Autonomous), Kollam, Kerala, India;3. Department of Chemistry, Mangalore University, Mangalagangothri, Karnataka, India;4. Department of Industrial Chemistry, Mangalore University, Mangalagangothri, Karnataka, India;5. University of Novi Sad, Faculty of Sciences, Department of Physics, Trg D. Obradovića 4, 21000 Novi Sad, Serbia;6. University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg D. Obradovića 3, 21000 Novi Sad, Serbia;7. Department of Chemistry, Arinagar Anna Government Arts College, Musiri PO, Thiruchirapalli, Tamilnadu, India;8. Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, B-2020, Antwerp, Belgium;9. Department of Chemistry, P.A.College of Engineering, Nadupadavu, Mangaluru, Karnataka, India;1. Department of Chemistry, Karnatak University, Dharwad, 580003, Karnataka, India;2. Dr. Prabhakar Kore Basic Science Research Center, KLE University, Belgaum 590010, Karnataka, India;3. KLE University''s College of Pharmacy, Nehru Nagar, Belgaum 590010, Karnataka, India;4. Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, S.E.T.''s College of Pharmacy, Sangolli Rayanna Nagar, Dharwad-580002, Karnataka, India;5. Department of Chemistry, G.S.S. College, Belagavi, Karnataka, India |
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| Abstract: | Reported herein are the design, synthesis, and pharmacologic evaluation of novel pyrazole and pyrazoline derivatives. The study presents the effect of lengthening of carbon chain in different pyrazole derivatives bearing various amine moieties. Combination of pyrazoline ring with either pyrazole or quinoline rings (Floctafenine derivatives) through synthesis of chalcones and their cyclization into pyrazolines was involved. The structures of target compounds were confirmed by elemental analysis and spectral data. All the newly synthesized compounds were investigated for their anti-inflammatory and analgesic activities compared to Indomethacin as a reference drug. Docking and molecular modeling study was initiated to validate the attained pharmacological data and provide understandable evidence for the observed anti-inflammatory behavior of the most potent compounds 14b, 15b and 22 through their various interactions with the active site of COX-2 isozyme. Protein Data Bank (PDB) file of COX II enzyme with the code 4Z0L and its co-crystallized ligand Indomethacin were used for this purpose. The binding affinity was evaluated via comparing the scoring energy (S) and amino acid interactions of novel compounds with Indomethacin. |
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| Keywords: | Pyrazole Floctafenine Anti-inflammatory Analgesic Chalcones Indomethacin Docking Molecular modeling study |
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