Design and synthesis of phenanthridinone and phenanthridine derivatives and their radiosensitizing activity

Abstract

To find novel radiosensitizers, a series of phenanthridinone and phenanthridine derivatives were designed and synthesized based on the structural simplification strategy from the natural product oxynitidine scaffold. Colony formation assays indicated that the phenanthridine derivative B9 showed strong radiosensitizing activity in colorectal cancer HCT116 cells in a concentration- and dose-dependent manner. Further investigations revealed that B9 could increase intracellular ionizing radiation-induced ROS levels and DNA damage, and induce cancer cell apoptosis and cycle arrest at G2/M phase. These results suggest that phenanthridine chemotype is a novel scaffold for the discovery of radiosensitizers.