Synthesis, Anticancer Activity, Pharmacokinetics, and Docking Study of Some New Heterocycles Linked Indole Moiety

A novel series of five or six new nitrogenated heterocyclic compounds were obtained by reacting a chalcone derivative of 3-acetylindole with various reagents such as malononitrile under different conditions, some hydrazine derivatives, some cyclic and heterocyclic amines, ethyl cyanoacetate, and urea. Elements analysis and spectral data were used to validate the newly synthesized compounds. Also, they were tested for their anticancer activity against three cancer cell lines including MCF7, HCT116, and HeLa cell lines, cells were subjected to treatment with one concentration (10uM) of compounds over 48 h incubation. Furthermore, a docking study was carried out to investigate the interaction of the newly prepared derivatives with vascular endothelial growth factor-2 tyrosine kinase (VEGFR-2) for their cancer-fighting potential. The docking study results showed that six indolyl derivatives (7 b, 9, 10, 11, 12, and 17) had high docking scores and a strong fitting interaction in the active site of vascular endothelial growth factor-2 tyrosine kinase (VEGFR-2). Furthermore, the pharmacokinetics and physicochemical properties, as well as drug-likeness and bioactivity, were investigated and analyzed.

Automated summary

A series of new nitrogenated heterocyclic compounds were successfully synthesized by reacting a chalcone derivative of 3-acetylindole with various reagents. The newly synthesized compounds were validated using elements analysis and spectral data. They exhibited promising anticancer activity and strong binding interaction with the active site of vascular endothelial growth factor-2 tyrosine kinase (VEGFR-2), indicating their potential as anticancer agents.