Synthesis and biological activity of new phenothiazine-based heterodimers

Abstract

10-(Chloroacetyl)phenothiazine reacted with 2-thioxo-1,2-dihydronicotinonitriles in the presence of KOH to form 2-{[2-oxo-2-(10H-phenothiazin-10-yl)ethyl]thio}nicotinonitriles or (3-aminothieno[2,3-b]pyridin-2-yl)(10H-phenothiazin-10-yl)methanones. Some of the synthesized compounds manifested herbicide safening effects against 2,4-D herbicide under conditions of laboratory experiments on sunflower seedlings. According to the results of molecular docking, the nicotinonitrile—phenothiazine heterodimers were found to be promising modulators of the PI3K/AKT/mTOR signaling pathway and of interest as potential antitumor agents.