Syntheses of LSD1/HDAC Inhibitors with Demonstrated Efficacy against Colorectal Cancer: In Vitro and In Vivo Studies Including Patient-Derived Organoids.

ABSTRACT: Precedential evidence ascertaining the overexpression of LSD1 and HDACs in colorectal cancer spurred us to design a series of dual LSD1-HDAC inhibitors. Capitalizing on the modular nature of the three-component HDAC inhibitory model, tranylcypromine as a surface recognition motif was appended to zinc-binding motifs via diverse linkers. A compendium of hydroxamic acids was generated and evaluated for in vitro cytotoxicity against HCT-116 cells (human colorectal cancer cell lines). The most potent cell growth inhibitor 2 (GI₅₀ = 0.495 μMm HCT-116 cells) shows promising anticancer effects by reducing colony formation and inducing cell cycle arrest in HCT-116 cells. It exhibits preferential inhibition of HDAC6, along with potent inhibition of LSD1 compared to standard

SUBMITTER: Chou PY 

PROVIDER: S-EPMC11472331 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature