Design,synthesis of celecoxib-tolmetin drug hybrids as selective and potent COX-2 inhibitors |
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| Affiliation: | 1. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Fayoum University, Fayoum 63514, Egypt;2. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni Suef University, Beni Suef 62514, Egypt;3. College of Pharmac, Al Jouf University, Sakaka, Al jouf 2014, Saudi Arabia;4. Department of Zoology, Faculty of Science, Beni Suef University, Beni Suef 62514, Egypt;5. Pharmaceutical Sciences Department, Ibn Sina National College for Medical Studies, Jeddah 21418, Kingdom of Saudi Arabia;1. Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Al Jouf-2014, Saudi Arabia;2. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt;3. Chemistry Department, Faculty of Science, Jouf University, P.O. Box, 2014, Aljouf, Saudi Arabia;4. Chemistry Department, Faculty of Science, Zagazig University, Zagazig, Egypt;5. Department of Pharmacology and Toxicology, Beni-Suef University, Beni-Suef 62514, Egypt;1. Dipartimento di Biotecnologie, Chimica e Farmacia, (Dipartimento d’Eccellenza 2018-2022), Università di Siena, Via A. Moro, I-53100 Siena, Italy;2. Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, I-56126 Pisa, Italy;3. Dipartimento di Scienze della Vita, Università di Siena, Via A. Moro, I-53100 Siena, Italy;4. Dipartimento di Farmacia, (Dipartimento d’Eccellenza 2018-2022), Scuola di Medicina e Chirurgia, Università di Napoli “Federico II”, Via D. Montesano 49, I-80131 Napoli, Italy;5. Dipartimento di Neuroscienze, Area del Farmaco e Salute del Bambino (NEUROFARBA), Università di Firenze, Viale G. Pieraccini 6, I-50139 Firenze, Italy;1. Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt;2. Pharmacology Department, Faculty of Veterinary, Cairo University, Cairo, Egypt |
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| Abstract: | Three novel series of diarylpyrazole 10b-d and triarylpyrazole derivatives 11a-d &12a-d were synthesized through Vilsmier-Haack condition. The structures of prepared compounds were determined through IR, 1H NMR, 13C NMR, Mass spectral and elemental analysis. Docking of the synthesized compounds over COX-2 active site ensure their selectivity. Moreover, the target compounds were evaluated for both in vitro and in vivo inhibitory activity. All compounds were more selective for COX-2 isozyme than COX-1 isozyme and with excellent anti-inflammatory activity. Compounds 11b, 11d and 12b showed the highest anti-inflammatory activity (67.4%, 62.7%, 61.4% respectively), lower ulcerogenic liability (UI = 2.00, 2.75, 3.25 respectively) than indomethacin (UI = 14) and comparable to celecoxib (UI = 1.75) which were confirmed from the histopatholgical study. |
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| Keywords: | Tolmetin analogues Triarylpyrazole COX-2 Celecoxib Anti-inflammatory |
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