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

Autor: Abd El-Lateef HM; Department of Chemistry, College of Science, King Faisal University Al-Ahsa 31982 Saudi Arabia hmahmed@kfu.edu.sa.; Department of Chemistry, Faculty of Science, Sohag University Sohag 82524 Egypt., Gaafar A; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Port Said University Port Said Egypt., Alqahtani AS; Department of Chemistry, College of Science, Imam Mohammad Ibn Saud Islamic University(IMSIU) P.O. Box 90950 Riyadh 11623 Saudi Arabia., Al-Mutairi AA; Department of Chemistry, College of Science, Imam Mohammad Ibn Saud Islamic University(IMSIU) P.O. Box 90950 Riyadh 11623 Saudi Arabia., Alshaya DS; Department of Biology, College of Science, Princess Nourah bint Abdulrahman University P.O. Box 84428 Riyadh 11671 Saudi Arabia., Elsaid FG; Department of Biology, College of Science, King Khalid University PO Box 960 Abha 61421 Asir Saudi Arabia., Fayad E; Department of Biotechnology, College of Sciences, Taif University P.O. Box 11099 Taif 21944 Saudi Arabia., Farouk NA; Department of Chemistry, Faculty of Science, Port Said University Port Said Egypt nesmafarouk566@gmail.com.
Jazyk: angličtina
Zdroj: RSC advances [RSC Adv] 2024 Aug 07; Vol. 14 (34), pp. 24781-24790. Date of Electronic Publication: 2024 Aug 07 (Print Publication: 2024).
DOI: 10.1039/d4ra04915b
Abstrakt: 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.
Competing Interests: No potential conflict of interest was reported by the author(s).
(This journal is © The Royal Society of Chemistry.)
Databáze: MEDLINE
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