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Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

Research Article

Design, Synthesis and Biological Screening of Some Pyridinylpyrazole and Pyridinylisoxazole Derivatives as Potential Anti-inflammatory, Analgesic, Antipyretic and Antimicrobial Agents

Author(s): Soad A.M. El-Hawash, Raafat Soliman, Amal M. Youssef, Hanan M.A. Ragab, Perihan A.S. Elzahhar, Ibrahim M. El-Ashmawey, Abeer E. Abdel Wahab and Iman A. Shaat

Volume 10, Issue 3, 2014

Page: [318 - 338] Pages: 21

DOI: 10.2174/15734064113096660044

Price: $65

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Abstract

A series of substituted pyridinylpyrazole (or isoxazole) derivatives were synthesized and evaluated for their anti-inflammatory (AI) activity using formalin-induced paw edema bioassays. Their inhibitory activities of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2) were also determined. The analgesic activity of the same compounds was evaluated using rat-tail withdrawal technique. Their antipyretic activity was also evaluated. The results revealed that compounds 4a,b, 6a, 8a, 14c and 15a exhibited significant AI and analgesic activities. Compounds 5a, 6a and 8a displayed good antipyretic activity. Compounds 14c and 15a showed good COX-2 inhibitory activity and weak inhibition of COX-1. Additionally, the most active compounds were shown to have a large safety margin (ALD50 >300-400 mg / Kg) and minimal ulcerogenic potentialities when administered orally at a dose of 300 mg/Kg. Docking studies for 14c and 15a with COX-2 showed good binding profile. Antimicrobial evaluation proved that most of the compounds exhibited distinctive activity against the gram negative bacteria, P. aeruginosa and E coli.

Keywords: Pyridinylpyrazoles, pyridinylisoxazoles, anti-inflammatory activity, analgesic activity, antipyretic activity, antimicrobial activity.


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