New thiazolo-quinolone hybrids as EGFR and/or PI3K inhibitors and as apoptosis inducers via modulating Bax/Bcl-2/p53 cascade

• Published in: Monatshefte für Chemie 2024-11, Vol.155 (11), p.1131-1143
• Main Authors: Mohamed, Asmaa H., Aly, Ashraf A., Alshammari, Mohammed B., Ahmad, Akil, Balboul, Basma A. A., Ghareeb, Doaa A., Abdelaziz, Marwa E., El-Agroudy, Eman J.
• Format: Article
• Language: English
• Subjects: Analytical Chemistry; Apoptosis; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Growth factors; Inorganic Chemistry; Kinases; Organic Chemistry; Original Paper; Physical Chemistry; Theoretical and Computational Chemistry
• ISSN: 0026-9247; 1434-4475
• DOI: 10.1007/s00706-024-03259-4

New hybrids of 4-aminothiazolo-2-quinolone-5-carbonitriles were synthesized and assessed for their antiproliferative activity against lung and colon cancer cell lines (A549 and Caco-2, respectively) in addition to normal human cells (WI-38) using MTT assay and sorafenib as reference drug. Five derivatives exhibited high potency and selectivity for A549 cancer cells. The active candidates promoted apoptosis of lung cancer cells through expression of Bax, Bcl-2, p53, EGFR, PI3K, and mTOR signaling pathway as suggested by RT-PCR data. Moreover, in vitro enzymatic inhibition assays of epidermal growth factor receptor (EGFR) and phosphoinositol 3-kinase (PI3K) were performed. A 6-methoxy-2-quinolone derivative demonstrated inhibition of EGFR comparable to that of gefitinib while a 1-ethyl-2-dihydroquinolone derivative showed significant inhibition to PI3K higher than buparlisib. Graphical Abstract