Design, synthesis, and antiproliferative screening of new quinoline derivatives bearing a cis-vinyl triamide motif as apoptosis activators and EGFR-TK inhibitors

HM Abd El-Lateef, A Gaafar, AS Alqahtani… - RSC …, 2024 - pubs.rsc.org
In this work, a congeneric set of quinoline-tethered cis-vinyl triamide hybrids was prepared
and evaluated as EGFR tyrosine kinase inhibitors for the management of breast cancer. All
of the prepared hybrids were evaluated for their antiproliferative effect against the breast
MCF-7 cell line. Among the tested hybrids, compound 6f displayed the most potent
antiproliferative activity with an IC50 value of 1.87 μM compared to STU (IC50= 13.71 μM) as
the standard reference. The most promising hybrid, 6f, was found to induce cellular cycle …
In this work, a congeneric set of quinoline-tethered cis-vinyl triamide hybrids was prepared and evaluated as EGFR tyrosine kinase inhibitors for the management of breast cancer. All of the prepared hybrids were evaluated for their antiproliferative effect against the breast MCF-7 cell line. Among the tested hybrids, compound 6f displayed the most potent antiproliferative activity with an IC50 value of 1.87 μM compared to STU (IC50 = 13.71 μM) as the standard reference. The most promising hybrid, 6f, was found to induce cellular cycle arrest at the G1 phase. Furthermore, the molecular mechanism of this hybrid revealed its ability to induce cellular apoptosis via the mitochondrial-dependent apoptotic pathway. Compound 6f decreased MCF-7 cells' MMP compared to the controls (percentage change value of 57.93%). Further investigation of the selective compound 6f showed that it can inhibit EGFR tyrosine kinase.
The Royal Society of Chemistry
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