Novel indole α-methylene-γ-lactones as potent inhibitors for AKT-mTOR signaling pathway kinases

In an effort to generate novel anticancer agents, a series of hybrids of α-methylene-γ-lactones and 2-phenyl indoles has been synthesized and evaluated for inhibition activities on the phosphorylation of AKT, mTOR, p70S6 kinase, and 4E-BP1. The results indicate that substitutes on the γ-position of lactones have a rather significant influence on inhibition activities.

Graphical abstractA novel series of indole α-methylene-γ-lactones with remarkable inhibition ability on phosphorylation of AKT, mTOR, p70S6 kinase, and 4E-BP1 has been synthesized.Figure optionsDownload full-size imageDownload as PowerPoint slide