الفهرس 
Dedication
Scope of InvestigationOnly 14 pages are availabe for public view
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Abstract
The design of the work is based on hybridization of 2-indolinone and 4-thiazolidinone /thiazolidinene moieties in one molecule utilizing structure-based drug design strategy using MOE 2020.09 software. Accordingly, synthesis of two series of the final compounds (Z)-3-substituted-2-(((E/Z)-5-substituted-2-oxo-1-substituted-indolin-3-ylidene)-hydrazinylidene)thiazolidin-4-ones, 4(a-z) and (E/Z)-1-substituted-3-(((Z)-3-substituted-4-methylthiazol-2(3H)-ylidene) hydrazineylidene)-5-substituted-indolin-2-ones, 5(a-q) were undertaken. Final compounds are present in two diastereomers (E/Z) forms, and either purified as a mixture (E/Z) or resolution on silica gel column using the appropriate developing system.Cytotoxicity of the target compounds 4(a-z) and 5(a-q) were tested in vitro against three cell lines, human liver cancer cell (HepG2), breast cancer cell (MCF-7), and human colon cancer cell (HCT-29) in addition to the diploid human normal cells (WI-38), doxorubicin was used as a reference drug. The tested molecules showed variable cytotoxic effects on the three cancer cell lines (IC50 2.59 – 100 micromole) with pronounced selectivity compared to the normal one. The most active compounds, with IC50 2.59 – 9.17 micromole, were subjected for further testing on the expression of four genes: p53, cyclin dependant kinase 2 (CDK2), caspase 3, and topoisomerase II (TopoII) in HepG2 cells as cell cycle key genes. As a general pattern the tested compounds elevated the expression of p53 and caspase3 by 4-5 folds and downregulated the expression of CDK2 and TopoII by 47 - 56%, compared to untreated cells. It is apparent that these compounds exert their antiproliferative activity through multiple cellular targets.