الفهرس 
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Abstract
The present thesis deals with the synthesis of new1-(4-chlorophenyl)-5-phenyl-1H-1,2,4-triazole-3-carboxamide derivatives and evaluation of their anti-inflammatory, anticonvulsant activity, inhibitory activity against TACEand their binding mode to the enzyme. The thesis includes four main parts; introduction, scope of investigation, results and discussion, and experimental one.
The first part “introduction” presents an overview about the biological activities of triazoles and a brief review about histone deacetylase inhibitors, tubulin polymerization inhibitors, TNF-α and its role in inflammatory diseases, TNF-α converting enzyme (TACE), different classes of TACEIs and the design of selective inhibitors. It also states the most common anticonvulsants, their mechanism of action and their structure activity relationship.
The second part “scope of investigation” outlines the main goals of this work, including the synthesis and biological evaluation of new 1,2,4-triazole-3-carboxamide derivatives.
The third part entitled “results and discussion” is subdivided into two sections.
A. Chemistry, which includes the processes employed in the synthesis of 1,5-diphenyl-1H-1,2,4-triazole-3-carboxamides and 1-(3,4,5-trimethoxyphenyl)-5-phenyl-1H-1,2,4-triazole-3-carboxamides
B. Evaluation of the biological activities of the synthesized compounds and it is subdivided into seven parts;
i) Evaluation of the in vivo anti-inflammatory activity of the synthesized compounds using indomethacin, celecoxib and ibuprofen as reference drugs. The results revealed that several synthesized 1,2,4-triazole-3-carboxamides induced significant anti-inflammatory activity compared to indomethacin.
ii) Evaluation of the ulcerogenic liability after intraperiotonial administration of the synthesized compounds, indomethacin, celecoxib or ibuprofen. The results revealed that the synthesized compounds exhibit safer ulcerogenic liability relative to indomethacin.
iii) Histopathological investigation of the ulcerative regions of stomach of the rats treated with the synthesized compounds. It was noted that very low incidence of gastric ulceration was induced by the tested compounds that was proved by the ulcerative index lower than 1.
iv) Evaluation of in vitro anti-inflammatory activity of compounds 10a, 11c, and 11g against Jurkat, Clone E6-1. IC50 of all compounds were in μM range and IC50 of most potent compound 5awas 0.23 μM.
v) Evaluation of TACE inhibitory activity, compounds 10a, 11c, and 11g were evaluated for their ability to inhibit TACE enzymatic activity and compared to that of control; In vitro TACE inhibition studies showed that all tested compounds are potent TACEIs with enzyme inhibition more than 80%.
vi) Docking studies of compounds10a, 11c, and 11g showed good binding of 10a, 11c, and 11g comparable to that of reference hydroxamate at the TACE active site.
vii) In evaluation of the anticonvulsant activity, seven compounds were selected for evaluation of anticonvulsant activity in both maximal elecroshock (MES) and chemoshock methods. Neurotoxicity was assessed in the rotarod test. In MES model, all compounds show parallel activity pattern to phenytoin and ester compound 6a showed more protection than phenytoin. In chemoshock, compound 4o showed higher activity than sodium valproate. Most target compounds showed no or minimal neurotoxicity.
The fourth major part, experimental, is divided into two sections; chemistry section and biological evaluation section