Design,synthesis of 2,3-disubstitued 4(3H)-quinazolinone derivatives as anti-inflammatory and analgesic agents: COX-1/2 inhibitory activities and molecular docking studies |
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| Affiliation: | 1. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia;2. Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt;3. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt;4. Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia;5. Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, AlKharj, Saudi Arabia;6. Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt;1. Department of Pharmaceutical Chemistry, R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Dhule, 425405 Maharashtra, India;2. Department of Pharmaceutical Chemistry, H.R. Patel College of Pharmacy, Shirpur, Dhule, 425405 Maharashtra, India;1. Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan;2. Department of Biochemistry, Hazara University, Garden Campus, Mansehra, Pakistan;3. Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan;4. Department of Bioinformatics and Biotechnology, International Islamic University, Islamabad 44000, Pakistan;5. Department of Chemistry, Allama Iqbal Open University, Islamabad 44000, Pakistan;1. College of Chemistry & Chemical Engineering, Shaanxi University of Science & Technology, Xi’an 710021, PR China;2. Key Laboratory of Auxiliary Chemistry & Technology for Chemical Industry, Ministry of Education, Xi’an 710021, PR China;3. Institute of Theoretical and Simulational Chemistry, Academy of Fundamental and Interdisciplinary Science, Harbin Institute of Technology, Harbin 150080, PR China;1. Department of Chemistry, University of Sargodha, Sargodha, Pakistan;2. Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan;3. School of Science & Engineering, Teesside University, Tees Valley, Middlesbrough TS1 3BA, UK;4. Department of Pharmacy, University of Malakand, Chakdara 18000, Dir (L), Pakistan;1. Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India;2. Medicinal Chemistry and Biotechnology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India;3. Pharmacology and Toxicology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India;1. Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431004, Maharashtra, India;2. School of Life Sciences, University of Hyderabad, Hyderabad, India |
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| Abstract: | A new series, 2-substituted mercapto-3-[2-(pyridin-2-yl)ethyl]-4(3H)-quinazolinone 1–21, was synthesized and evaluated for in vivo anti-inflammatory and analgesic activities and in vitro COX-1/COX-2 inhibition. Compounds 1, 4, 5, 6, 8, 10, 13, 14, 15, 16, and 17 exhibited potent anti-inflammatory and analgesic properties, with ED50 values of 50.3–112.1 mg/kg and 12.3–111.3 mg/kg, respectively. These values may be compared with those of diclofenac sodium (ED50 = 112.2 and 100.4 mg/kg) and celecoxib (ED50 = 84.3 and 71.6 mg/kg). Compounds 4 and 6 possessed strong COX-2 inhibitory activity with IC50 (0.33 μM and 0.40 μM, respectively) and selectivity index (SI > 303.0 and >250.0, respectively) values that are similar to those of the reference drug celecoxib (IC50 0.30 μM and COX-2 SI > 333). Compounds 5, 8, and 13 demonstrated effective COX-2 inhibitory activity with IC50 values of 0.70–0.80 μM and COX-2 SI > 125–142. Potent COX-2 inhibitors, such as compounds 4, 6, and 13, were docked into the active site pockets of COX-1 and COX-2, with the greatest recognition occurring at the COX-2 binding site and insignificant interactions at the binding site of the COX-1 pocket. |
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| Keywords: | Synthesis Anti-inflammatory activity COX-1/COX-2 inhibition assay Docking study |
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