Abstract
Bromodomain protein 4 (BRD4) plays a crucial role in transcriptional regulation and is considered to be a viable drug target for cancer treatment. Herein, we designed and synthesized a series of indole-2-one derivatives through scaffold hopping drug design. Most of the compounds showed potent BRD4 inhibitory activities and anti-proliferation activities in cancer cell lines. Especially, compound 12j exhibited excellent BRD4 inhibitory activities (BD1 IC50=19nM, BD2 IC50=28nM) and anti-proliferation potency with IC50 values of 4.75μM and 1.35μM in HT-29 and HL-60cells, respectively. Additionally, docking studies showed that the hydrophobic pocket next to KAc region and WPF shelf were critical to the activity of the compound. Compound 12j could arrest the cell-cycle progression of HT-29cells into the G1 phase and reduce the expression of c-Myc. Moreover, compound 12j exhibited favorable oral pharmacokinetic properties. All the results demonstrated that compound 12j was a potent BRD4 inhibitor and had merely potential for colon cancer treatment.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
