Design, Synthesis, and Biological Examination of N-Phenyl-6-fluoro-4-hydroxy-2-quinolone-3-carboxamides as Anticancer Agents

Cancer is one of the leading causes of death worldwide, and it has a major impact on public health. Phosphatidylinositol 3-kinase (PI3K alpha) has been recognized as a promising drug target for developing anticancer agents. Herein, a series of N-phenyl-6-fluoro-4-hydroxy-2-quinolone-3-carboxamides was developed to target PI3K alpha. All synthesized compounds were characterized using FT-IR, NMR (1H and 13C) and elemental analysis. All synthesized chemical analogues exerted distinctive anticancer activity. They inhibited the growth of human epithelial colorectal acienocarcinoma (Caco-2) with IC50 values between 48.63-378 mu M, and human colon cancer (HCT-116) cell lines with values between 44-664 mu M. Computational modelling studies provided important biological insight. Induced-fit docking (IFD) studies showed that the synthesized chemical analogues fit the kinase catalytic domains and form a significant H-bond interaction network with key amino acids at the biding site. Furthermore, cheminformatics analyses indicated that all synthesized compounds were drug-like permitting further animal testing or clinical development.

Automated summary

In this study, a series of compounds targeting PI3K alpha were developed, and they exhibited distinct anticancer activity against cancer cells. Computational modeling studies revealed the interaction between these compounds and key amino acids, as well as their drug-like properties. These findings provide important biological insights for further development of anticancer drugs.