AbdElhameid, Mohammed K. Labib, Madlen B. Negmeldin, Ahmed T. Al-Shorbagy, Muhammad Mohammed, Manal R. Design, synthesis, and screening of <i>ortho-</i>amino thiophene carboxamide derivatives on hepatocellular carcinomaas VEGFR-2Inhibitors <p>In this work, design, synthesis, and screening of thiophene carboxamides <b>4–13</b> and <b>16–23</b> as dual vascular endothelial growth factor receptors (VEGFRs) and mitotic inhibitors was reported. All compounds were screened against two gastrointestinal solid cancer cells, HepG-2 and HCT-116 cell lines. The most active cytotoxic derivatives <b>5</b> and <b>21</b> displayed 2.3- and 1.7-fold higher cytotoxicity than Sorafenib against HepG-2 cells. Cell cycle and apoptosis analyses for compounds <b>5</b> and <b>21</b> showed cells accumulation in the sub-G1 phase, and cell cycle arrest at G2/M phase. The apoptotic inducing activities of compounds <b>5</b> and <b>21</b>were correlated to the elevation of p53, increase in Bax/Bcl-2 ratio, and increase in caspase-3/7.Compounds <b>5</b> and <b>21</b> showed potent inhibition againstVEGFR-2 (IC<sub>50</sub> = 0.59 and 1.29 μM) and β-tubulin polymerization (73% and 86% inhibition at their IC<sub>50</sub> values).Molecular docking was performed with VEGFR-2 and tubulin binding sites to explain the displayed inhibitory activities.</p> Gastrointestinal carcinoma;HepG-2;HCT-116;thiophene carboxamide;β-tubulin;angiogenesis 2018-09-07
    https://tandf.figshare.com/articles/journal_contribution/Design_synthesis_and_screening_of_i_ortho-_i_amino_thiophene_carboxamide_derivatives_on_hepatocellular_carcinomaas_VEGFR-2Inhibitors/7058210
10.6084/m9.figshare.7058210.v1