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Drug Res (Stuttg) 2013; 63(06): 271-281
DOI: 10.1055/s-0032-1333293
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Design, Synthesis and Evaluation of some Novel Pyrazoline Derivatives as Potential Anti-inflammatory and Antitumor Agents[*]

R. Y. Elbayaa
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Alexandria, Alexandria, Egypt
,
M. H. Badr
2   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Alexandria, Alexandria, Egypt
,
A. A. Khalil
3   Department of Protein Technology, Institute of Genetic Engineering and Biotechnology, City for Scientific Research, New Borg Elarab, Alexandria, Egypt
,
M. Abdelhadi
4   Department of Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
› Author Affiliations
Further Information

Publication History

received 29 March 2012

accepted 25 December 2012

Publication Date:
12 April 2013 (online)

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Abstract

A new series of pyrazoline derivatives was designed and synthesized with the objective of developing agents with anti-inflammatory activity together with chemoprevention of hepatobiliary malignancies. The prepared compounds were evaluated for their anti-inflammatory activity using carrageenan-induced granuloma bioassay, using celecoxib as a reference drug. Ulcerogenic effect and acute toxicity profiles (ALD50) for the most active compounds were also determined. Compound 5c was proved to display anti-inflammatory activity better than celecoxib. Compounds 4b, 5d, 5c and 8 were found to be safer than indomethacin with respect to ulcerogenic effect and were well tolerated by the experimental animals with high safety margin (ALD50 >300 mg/Kg). Moreover, histopathological examination was carried out to detect the anti-inflammatory effect of the tested compounds on the livers of carrageenan-injected rats. On the other hand, compounds 4b, 4c, 4d, 5b, 5c, 5d, 6a, 6b, 6c, 6d, 8 and 9 were selected by the NCI to be evaluated for their anticancer activities but none has passed to the 5-dose assay. In addition, the ligand-receptor interactions of the most active compounds with COX-2 were investigated by performing docking studies using Molecular Operating Environment (MOE) version 2008.10.

Key words

pyrazoline - synthesis - design - anti-inflammatory activity - histopathology - malignancies - docking
*

* A part of the work was presented at Orchem 2010, Weimar, Germany in September 2010.


 

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