Abstract
Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies and is a leading cause of cancer‑related mortality worldwide. Histone deacetylases (HDACs) are a class of enzymes responsible for the epigenetic regulation of gene expression. Some HDAC inhibitors have been shown to be efficient agents for cancer treatment. The aim of the present study was to discover a novel, potent HDAC inhibitor and demonstrate its anticancer effect and molecular mechanisms in CRC cells. A novel fluorinated aminophenyl‑benzamide‑based compound, CBUD‑1001, was designed to specifically target HDAC1, and it was then synthesized and evaluated. CBUD‑1001 exerted a potent inhibitory effect on HDAC enzyme activity and exhibited anticancer potency against CRC cell lines. Molecular docking analysis rationalized the high potency of CBUD‑1001 by validating its conformation in the HDAC active site. Further investigation using CRC cells demonstrated that CBUD‑1001 inhibited HDAC activity by hyper‑acetylating histones H3 and H4, and it exerted an apoptotic effect by activating a mitochondrial‑dependent pathway. Of note, it was found that CBUD‑1001 attenuates the cell motility of CRC cells by downregulating the EMT signaling pathway. Thus, CBUD‑1001 may prove to be a promising novel drug candidate for CRC therapy.