Design, synthesis and biological evaluation of dual mTOR/HDAC6 inhibitors in MDA-MB-231 cells.

Basic Information

ID: ALA4811304

Journal: Bioorg Med Chem Lett

Title: Design, synthesis and biological evaluation of dual mTOR/HDAC6 inhibitors in MDA-MB-231 cells.

Authors: Yao D, Jiang J, Zhang H, Huang Y, Huang J, Wang J.

Abstract: The excessive activation of histone deacetylase (HDAC) and mammalian target of rapamycin (mTOR) signaling promotes tumor growth and progression. We proposed that dual targeting mTOR and HDAC inhibitors is a promising strategy for triple negative breast cancer (TNBC) treatment. In this study, a series of dual mTOR/HDAC6 inhibitors were designed and synthesized by structure-based strategy. 10g was documented to be a potent dual mTOR/HDAC6 inhibitor with IC50 value of 133.7 nM against mTOR and 56 nM against HDAC6, presenting mediate antiproliferative activity in TNBC cells. Furthermore, we predicted the binding mode of 10g and mTOR/HDAC6 by molecule docking. In addition, 10g was documented to induce significant autophagy, apoptosis and suppress migration in MDA-MB-231 cells. Collectively, these findings revealed that 10g is a novel potent dual mTOR/HDAC6 inhibitor, which provides promising rationale for the combination of dual mTOR/HDAC6 inhibitors for TNBC treatment.

CiteXplore: 34139324

DOI: 10.1016/j.bmcl.2021.128204

Patent ID: