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

• Published in: RSC advances 2024-08, Vol.14 (34), p.24781-2479
• Main Authors: Abd El-Lateef, Hany M, Ahmed Gaafar, Ahmed Gaafar, Alqahtani, Arwa Sultan, Al-Mutairi, Aamal A, Alshaya, Dalal Sulaiman, Elsaid, Fahmy Gad, Fayad, Eman, Farouk, N. A
• Format: Article
• ISSN: 2046-2069
• DOI: 10.1039/d4ra04915b

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 IC 50 value of 1.87 μM compared to STU (IC 50 = 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. A set of novel quinoline tethered cis -vinyl triamides derivatives has been designed, synthesized and screened for in vitro cytotoxicity against the MCF-7 breast adenocarcinoma cell line.