Design,synthesis and biological screening of some novel celecoxib and etoricoxib analogs with promising COX-2 selectivity,anti-inflammatory activity and gastric safety profile |
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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. International Chinese-Belorussian Scientific Laboratory on Vacuum-Plasma Technology, College of Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094, China;2. Francisk Skorina Gomel State University, 104, Sovetskaya Street, Gomel 246019, Belarus;1. Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, 33 El Bohouth St, Dokki, Giza 12622, Egypt;2. Department of Pharmaceutical Medicinal Chemistry and Drug Design, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11754, Egypt;3. Pharmacology Department, National Research Centre, 33 El Bohouth St, Dokki, Giza 12622, Egypt;4. Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt;2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Deraya University, Minia, Egypt;3. Graduate School of Organic Materials Science, Yamagata University, Jonan 4-3-16, Yonezawa 992-8510, Japan;4. Graduate School of Science and Engineering, Yamagata University, Yonezawa, Yamagata 992-8510, Japan;5. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo P.O. Box 11562, Egypt;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, 21521 Alexandria, Egypt;2. Pharmacology Department, Faculty of Veterinary Medicine, Alexandria University, Alexandria, Egypt;3. Department of Veterinary Medicine, Faculty of Agricultural and Veterinary Medicine, Qassim University, P.O. Box 1482, Buraydah, Al-Qassim, Saudi Arabia;1. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt;2. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt;3. Department of Pharmaceutical Chemistry, College of Pharmacy, Aljouf University, Aljouf, Sakaka2014, Saudi Arabia;4. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt;5. Department of Medicinal Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt;6. Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, Taif 21974, Saudi Arabia;7. Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Cairo, Egypt;8. Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Aljouf University, Aljouf, Sakaka2014, Saudi Arabia;9. Histology Department, Faculty of Medicine, Al-Azhar University, Damietta, Egypt;10. School of Natural and Computing Sciences, University of Aberdeen, Meston Building, Aberdeen, AB243UE, Ireland |
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| Abstract: | Two new series of 4,6-diaryl-3-cyanopyridine 4a-r and 1,3,5-triaryl-2-pyrazolines 6a-f and were prepared. The new compounds were evaluated for their in vitro COX-2 selectivity and in vivo anti-inflammatory activity. Compounds 4o,r and 6d,f had moderate to high selectivity index (S.I.) compared to celecoxib (selectivity indexes of 4.5, 3.14, 4.79 and 3.21, respectively) and also, showed in vivo anti-inflammatory activity approximately equal to or higher than celecoxib (edema inhibition % = 60.5, 64.5, 59.3 and 59.3, after 3 h, respectively) and the effective anti-inflammatory doses were (ED50 = 10.1, 7.8, 8.46 and 10.7 mg/kg respectively, celecoxib ED50 = 10.8 mg/kg) and ulcerogenic liability were determined for these compounds which showed promising activity by being more potent than celecoxib with nearly negligible ulcerogenic liability compared to celecoxib (reduction in ulcerogenic liability versus celecoxib = 85, 82, 74 and 67%, respectively). |
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| Keywords: | Pyrazoline Cyanopyridine Cyclooxygenase inhibition Anti-inflammatory |
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