Design,synthesis, cyclooxygenase inhibition and biological evaluation of new 1,3,5-triaryl-4,5-dihydro-1H-pyrazole derivatives possessing amino/methanesulfonyl pharmacophore |
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| Affiliation: | 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. Department of Pharmaceutical Chemistry, Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), Mehrauli-Badarpur Road, PushpVihar, Sector-3, New Delhi 110017, India;2. Faculty of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak 124001, India;1. Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt;2. Pharmaceutical Sciences Department, Ibn Sina National College for Medical Studies, Jeddah 21418, Saudi Arabia;3. Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt;4. Biochemistry Department, Cairo General Hospital, Cairo, Egypt;5. Pharmacology Department, Faculty of Veterinary, Cairo University, Cairo, Egypt;1. Department of Chemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India;2. Molecular Endocrinology and Toxicology Lab (MET Lab), Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India;3. Cadila Pharmaceutical Limited, Dholka, Gujarat 382225, India;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Nahda University, Beni-Suef 62517, Egypt;2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Abassia, Cairo 11566, Egypt;3. Department of Histology, Faculty of Medicine, Minia University, Minia 61519, Egypt;4. Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt |
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| Abstract: | A new series of 1,3,5-triaryl-4,5-dihydro-1H-pyrazole 10a–l was designed and synthesized via cyclization of chalcones 8a–f with 4-amino/methanesulfonylphenylhydrazine hydrochloride 9a–b. All the synthesized compounds were evaluated for their cyclooxygenase (COX) inhibition, anti-inflammatory activity, ulcerogenic liability and analgesic activity. All compounds were more COX-2 inhibitors than COX-1. While most compounds showed good anti-inflammatory activity, the trimethoxy derivatives (10a, 10b, 10g and 10h) were the most potent derivatives (ED50 = 55.78, 53.99, 67.65 and 69.20 μmol/kg respectively) in comparison with celecoxib (ED50 = 82.15 μmol/kg). Compounds 10a, 10b, 10g and 10h (ulcer index = 2.68, 1.20, 2.63 and 2.66 respectively) showed less ulceration effect than celecoxib (ulcer index = 2.90). Also, Compounds 10a, 10b, 10g and 10h showed analgesic activity higher than celecoxib and comparable to that of ibuprofen. In addition, molecular docking studies were performed for compounds 10a, 10b, 10g and 10h and the results were in agreement with that obtained from the in vitro COX inhibition assays. |
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| Keywords: | Anti-inflammatory Cyclooxygenase-2 inhibitors |
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