الفهرس 
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Abstract
The present study deals with the design and synthesis of novel spirohydantoin derivatives (series I), as well as 1,2,4-triazole-3-carboxamide derivatives (series II). It also includes evaluating their anti-proliferative, histone deacetylase (HDAC) inhibitory activities, tubulin polymerization inhibitory activities, and their binding modes to these proteins. The thesis includes four main sections
The first section “Introduction” presents a literature survey about histone deacetylase inhibitors (HDACIs) as potential anticancer entities. In addition a brief look over tubulin, and microtubule targeting agents (MTAs) and their anticancer and vascular disrupting properties. Moreover, an overview about tubulin-HDACI hybrids as a part of study multi-target drug design protocols is also provided. Also the introductory part includes an overview about the synthetic procedures of spirohydantoins, and their biological activities, as well as, an overview bout the synthetic procedures of 1,2,4-triazole derivatives and their various biological activities.
The second part “Scope of investigation” outlines the main goals and the rationale of this work, which includes the design and synthesis of novel spirohydantoin derivatives (series I) as potent antitumor compounds with HDAC inhibitory activity, as well as, designing and synthesizing novel 1,2,4-triazole-3-carboxamide derivatives as novel CA4 analogues that possesses a HDACIs pharmacophore serving as tubulin-HDAC dual inhibitors.
The third section “Results and discussion” describes the data obtained from the steps of the synthesis and biological evaluation of spirohydantoin and 1,2,4-triazole-3-carboxamide derivatives. This part is subdivided into two categories.
A) Chemistry, which includes the processes employed in the synthesis of spirohydantoin and 1,2,4-triazole-3-carboxamide derivatives. Structural proof of all newly synthesized compounds is based on IR, 1H NMR, and high resolution mass (HRMS) spectroscopy.
B) Biological evaluation, which deals with evaluation of the biological activities of the synthesized compounds including anti-proliferative activity, tubulin polymerization inhibitory activity, HDAC inhibitory activity, and Molecular modeling study. Most of tested compounds show high activity as well as good binding to enzymes justifies the experimental findings.
The fourth section, “Experimental”, includes the different procedures employed in synthesis of the targeted compounds, and their biological evaluation.