الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Background: The present study deals with the synthesis of new thiazole, thiazolopyrimidine and thiazolotriazine derivatives to be tested for their anticancer activity. Also, discusses the classification of anticancer kinase inhibitor drugs based on their binding mode in the kinase domain, also includes different examples of FDA approved anticancer benzimidazole kinase inhibitors and also those in different phases of clinical trials in addition to exploring the other FDA approved benzimidazole derivatives with different biological activities.Method: includes the synthetic procedures of the designed compounds as well as the physicochemical and spectral data of the prepared compounds and the adopted procedure for in vitro anticancer screening, as well as the methods of enzyme inhibition assays of VEGFR-2 and in vivo anticancer assay. Cell cycle analysis, apoptosis, caspases 3/9 and BAX/BCL-2 activities were also tested. Molecular modelling tools were also employed.Results: Compound 253 was proved to be the most potent compound against the five tested cell lines. In addition, compounds 252 and 254 showed strong activity against the five tested cancer cell lines. Whereas, compounds 259b, 264b and 271c displayed outstanding activity toward HepG2, HCT-116, MCF-7 and Hela cancer cell lines. The most active antitumor analogs 251-254, 259b, 264a,b, 267g, 269a and 271c were tested for their in vitro VEGFR-2 inhibitory activity. Results showed that compounds 253 and 271c have potent VEGFR-2 inhibitory activity. While, compounds 252, 264b and 267g showed good VEGFR-2 inhibitory activity. Furthermore, the most active antitumor compounds 252, 253, 259b and 271c were assessed for their in vivo antitumor activity. The four tested compounds showed decreased breast solid tumor volume in adult Swiss female albino mice after 5, 10, 15 and 20 days of treatment Conclusion: compound 253 exhibited the most potent antitumor activity over all screened cancer cells with the most potent VEGFR-2 inhibitory activity. Also, It increased BAX level and decreased BCL-2 level and showed strong VEGFR-2 binding affinity. While, compound 271c showed strong inhibitory activity over four tested cancer cells with strong VEGFR-2 inhibitory activity. Futhermore, it increased caspases 3/9 levels and showed the most potent VEGFR-2 binding affinity. So, compounds 253 and 271c can be considered as novel safe potent VEGFR-2 inhibitors with promising antitumor activity.