الفهرس 
Design, synthesis and molecular modeling study of some novel pyrazole derivatives as potential anticancer agents /
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Abstract
Cancer represents one of the main death causes worldwide. Despite the indispensable progress accomplished in cancer treatments, several limitations still exist. Subsequently, the innovation of novel small molecules that are both potent and selective remains a serious challenge to medicinal chemists. This thesis deals with the design and synthesis of some novel pyrazole and pyrazolopyridine derivatives which were evaluated as anticancer agents. In vitro CDK2 enzyme inhibition assay was carried out for all the final compounds. selectivity profile against a panel of other CDKs isoforms (CDK1, CDK4 and CDK7) was studied for the most promising compounds. Additionally, the uppermost active compounds were investigated for further mechanistic investigation; cell cycle analysis, apoptotic assay, and safety profile assessment. Molecular docking study was carried out to predict the possible binding mode of the newly synthesized compounds with the CDK2 ATP binding site in a trial to explain their observed activity. Moreover, a 2D QSAR model revealed the structural characteristics governing the CDK2 inhibition activity of our target pyrazolopyridine derivatives. Finally, ADMET computational study predicted the pharmacokinetic aspects and toxicity risks for the studied compounds