Synthesis and anti-inflammatory activity of sulfonamides and carboxylates incorporating trimellitimides: Dual cyclooxygenase/carbonic anhydrase inhibitory actions |
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| Institution: | 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. Università degli Studi di Firenze, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy;4. Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt;5. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa City, Egypt;1. Chemistry Department, Faculty of Arts and Science, Dumlup?nar University, 43100 Kütahya, Turkey;2. Università degli Studi di Firenze, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche e Nutraceutiche, 50019 Sesto Fiorentino (Florence), Italy;3. Biochemistry Department, Faculty of Arts and Science, Dumlup?nar University, 43100 Kütahya, Turkey;1. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia;2. Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt;3. Università degli Studi di Firenze, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy;4. Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt;1. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia;2. Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy;3. Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, AlKharj, Saudi Arabia;4. Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt;5. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt;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 Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt;4. NEUROFARBA Department, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Florence), Italy;1. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt;2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Horus University, New Damietta, Egypt;3. Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt;4. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa City, Egypt;5. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia;6. Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, 11884, Egypt;7. Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia;1. Department of Medicinal Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt;2. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt;3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt;4. Department of Medicinal Chemistry, Faculty of Pharmacy, Sinai University, Kantra, Egypt |
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| Abstract: | Trimellitimides 6–21 were prepared and investigated in vivo for anti-inflammatory and ulcerogenic effects and in vitro for cytotoxicity. They were subjected to in vitro cyclooxygenase (COX-1/2) and carbonic anhydrase inhibition protocols. Compounds 6–11 and 18 exhibited anti-inflammatory activities and had median effective doses (ED50) of 34.3–49.8 mg kg?1 and 63.6–86.6% edema inhibition relative to the reference drug celecoxib (ED50: 33.9 mg kg?1 and 85.2% edema inhibition). Compounds 6–11 and 18 were weakly cytotoxic at 10 μM against 59 cell lines compared with the reference standard 5-fluorouracil (5-FU). Compounds 6–11 had optimal selectivity against COX-2. The selectivity index (SI) range was >200–490 and was comparable to that for celecoxib COX-2 (SI) > 416.7]. In contrast, compounds 12, 13, and 16–18 were nonselective COX inhibitors with a selectivity index range of 0.92–0.25. The carbonic anhydrase inhibition assay showed that sulfonamide incorporating trimellitimides 6–11 inhibited the cytosolic isoforms hCA I and hCA II, and tumor-associated isoform hCA IX. They were relatively more susceptible to inhibition by compounds 8, 9, and 11. The KI ranges were 54.1–81.9 nM for hCA I, 25.9–55.1 nM for hCA II, and 46.0–348.3 nM for hCA IX. © 2018 Elsevier Science. All rights reserved. |
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| Keywords: | Trimellitimide Benzenesulfonamides Anti-inflammatory activity Cytotoxic activity COX-1/2 inhibition Carbonic anhydrase inhibition |
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