Browsing by Author "Sakr, Tamer M"

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    New 5-Aryl-1,3,4-Thiadiazole-Based Anticancer Agents: Design, Synthesis, In Vitro Biological Evaluation and In Vivo Radioactive Tracing Studies
    (Multidisciplinary Digital Publishing Institute (MDPI), 2022-11) El-Masry, Rana M; Essa, Basma M; Selim, Adli A; El-Emam, Soad Z; Mohamed, Khaled O; Sakr, Tamer M; Kadry, Hanan H; Taher, Azza T; Abou-Seri, Sahar M
    A new series of 5-(4-chlorophenyl)-1,3,4-thiadiazole-based compounds featuring pyri- dinium (3), substituted piperazines (4a–g), benzyl piperidine (4i), and aryl aminothiazoles (5a–e) heterocycles were synthesized. Evaluation of the cytotoxicity potential of the new compounds against MCF-7 and HepG2 cancer cell lines indicated that compounds 4e and 4i displayed the highest activity toward the tested cancer cells. A selectivity study demonstrated the high selective cytotoxicity of 4e and 4i towards cancerous cells over normal mammalian Vero cells. Cell cycle analysis revealed that treatment with either compound 4e or 4i induced cell cycle arrest at the S and G2/M phases in HepG2 and MCF-7 cells, respectively. Moreover, the significant increase in the Bax/Bcl-2 ratio and caspase 9 levels in HepG2 and MCF-7 cells treated with either 4e or 4i indicated that their cytotoxic effect is attributed to the ability to induce apoptotic cell death. Finally, an in vivo radioactive tracing study of compound 4i proved its targeting ability to sarcoma cells in a tumor-bearing mice model.
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    Pyrazolo[3,4-d]pyrimidine derivatives as EGFRT790M and VEGFR-2 dual TK inhibitors: Design, synthesis, molecular docking, ADMET profile and anticancer evaluations
    (Elsevier, 2023-06) Adel, Dina; El-Adl, Khaled; Nasr, Tamer; Sakr, Tamer M; Zaghary, Wafaa
    Seventeen new pyrazolo[3,4-d]pyrimidine derivatives have been designed, created and tested as dual VEGFR-2 and EGFR inhibitors for their anticancer special effects against A549, HepG2, MCF-7, and HCT-116. In order to determine how the proposed chemicals might interact to the EGFR and VEGFR-2 receptors, molecular docking was used for these derivatives. The data from the docking studies and the results of the biological screening had excellent correlation. Compounds 14 and 15 displayed the best effects against HepG2, while the derivatives 10d, 15 and 18 showed the greatest anticancer activity against MCF-7. Moreover, compounds 15 and 18 exhibited the greatest anticancer effects against HCT-116 but compound 18 exhibited the greatest anticancer effect against A549. Compound 18 exhibited higher activities than Sorafenib against MCF-7, HCT116 and A549 correspond- ingly but lower actions versus HepG2. However, this substance showed greater effects than erlotinib against MCF-7 and HCT116 but lesser effects against A549 and HepG2 in that order. Compound 15 shown lower ac- tivities versus A549 but higher activity against HepG2, MCF-7, and HCT116 than Sorafenib and Erlotinib. De- rivative 18 displayed higher effects as dual VEGFR-2 and EGFRT790M tyrosine kinases inhibitors more than both Sorafenib and Erlotinib respectively. Finally, our derivatives 10d, 15 and 18 demonstrated an excellent ADMET profile when calculated in silico. According to the results, our compounds could serve as a model for future creation, optimization, adaption, and research to create more powerful and selective dual VEGFR-2/EGFRT790M inhibitors with more anticancer potential.