Substituted thiazolidinone linked to benzothiazoles and benzoxazoles 3a,b or substituted 5-benzylidene-4- thiazolidinones 4a-h were synthesized. The antitumor activity of the prepared compounds was evaluated against human breast MCF7 and liver HEPG2 cancer cell lines using Sulphorhodamine-B (SRB) assay method, doxorubicin was used as a reference standard. Most of the tested compounds showed potent antitumor activity especially the pmethoxy- 5-benzylidine-4-thiazolidinone derivative of benzoxazole 4c and benzothiazole 4d, their IC50 against liver HEPG2 cancer cell line are 0.027 nM and 0.026 nM respectively. The IC50 of p-chloro-5-benzylidine-4- thiazolidinone linked to benzoxazole 4e against breast MCF7 cancer cell line, is 19 nM but, p-nitro-5-benzylidine- 4-thiazolidinone derivative of benzothiazole 4h showed a broad spectrum antitumor activity against MCF7 and HEPG2 cell lines, its IC50 is 36 and 48 nM respectively. The most active compounds were docked against VEGFR-2 using Moe program and 1Y6A (pdb file) to investigate if these compounds had a similar binding mode to VEGFR-2 inhibitors.