No abstract

The targeted approach of protein kinases (PKs), as PKs are the main regulators of cell survival and proliferation, has been a promising strategy for treatments for cancer. Here we analyze the potential of quinoline-carboximide derivatives for four cell lines: MCF-7, CACO, HepG-2 and HCT-116 as anticancer agents. 3e, 4b, 11b and 13d derivatives showed good anti-proliferative activities in comparison to the reference standard Doxorubicin, against the four cell lines tested. They have been chosen for further studies. First of all, the IC50 value surveys were carried out to ensure the protection of our hits and demonstrate that the cytotoxic effect (IC50 > 113 μM) is highly selective on normal human cells (WI-38). Secondly, apoptosis was accomplished by down-regulation of Bcl-2 and up-regulation of BAX and Caspase-3 by these active compounds. Also, the Pim-1 inhibitory activity of the active hybrids was done, which indicate that compound 3e was the most active with percentage of inhibition 82.27% and IC50 equal 0.11 when compaired to SGI-1776 as a reference standered. In addition, the in silico assessment of ADME properties, all of the strongest compounds are orally bioavailable without blood brain barrier penetration.

The targeted approach of protein kinases (PKs), as PKs are the main regulators of cell survival and proliferation, has been a promising strategy for treatments for cancer. Here we analyze the potential of quinoline-carboximide derivatives for four cell lines: MCF-7, CACO, HepG-2 and HCT-116 as anticancer agents. 3e, 4b, 11b and 13d derivatives showed good anti-proliferative activities in comparison to the reference standard Doxorubicin, against the four cell lines tested. They have been chosen for further studies. First of all, the IC50 value surveys were carried out to ensure the protection of our hits and demonstrate that the cytotoxic effect (IC50 > 113 μM) is highly selective on normal human cells (WI-38). Secondly, apoptosis was accomplished by down-regulation of Bcl-2 and up-regulation of BAX and Caspase-3 by these active compounds. Also, the Pim-1 inhibitory activity of the active hybrids was done, which indicate that compound 3e was the most active with percentage of inhibition 82.27% and IC50 equal 0.11 when compaired to SGI-1776 as a reference standered. In addition, the in silico assessment of ADME properties, all of the strongest compounds are orally bioavailable without blood brain barrier penetration.