A novel acridine derivative, LS-1-10 inhibits autophagic degradation and triggers apoptosis in colon cancer cells.

ABSTRACT: Autophagy promotes cancer cell survival and drug resistance by degrading harmful cellular components and maintaining cellular energy levels. Disruption of autophagy may be a promising approach to sensitize cancer cells to anticancer drugs. The combination of autophagic inhibitors, such as chloroquine (CQ) and lucanthone with conventional cancer therapeutics has been investigated in clinical trials, but adverse drug-drug interactions are a high possibility. Here we designed and synthesized a novel, small-molecule library based on an acridine skeleton and the CQ structure with various modifications and substitutions and screened the compounds for effective autophagy inhibition. We found that 9-chloro-2-(3-(dimethylamino)propyl)pyrrolo[2,3,4-kl]acridin-1(2H)-one (LS-1-10) was the most effecti

SUBMITTER: Fu W 

PROVIDER: S-EPMC5682664 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature