Chalcone Derivative B8HA as A Novel Histone Deacetylase and Tubulin Dual Inhibitors, Inhibits Triple-Negative Breast Cancer Cells Proliferation

Abstract

Designing and synthesizing dual- and multi-target drugs have raised considerable interests due to their advantages in improving potencies as antitumor agents. In previous studies, our group designed and synthesized a series of novel chalcone based tubulin and histone deacetylase (HDAC) dual-targeting inhibitors. Among them, compound B8HA exhibited promising potency for the treatment of triple-negative breast cancer. In this work, we highlighted its biological evaluations in MDA-MB-231 and 4T1 cells, including anti-proliferative effects, cell cycle arresting effects, anti-metastatic and anti-angiogenesis effects. In vivo results further demonstrated that B8HA significantly inhibited the 4T1 breast tumor growth and destroyed tumor blood vessel as compared to its counterparts. The results indicated that compound B8HA could be a potent inhibitor of both HDAC and tubulin, leading to excellent in vitro and in vivo antiproliferative activities, and is a promising therapeutic agent for triple-negative breast cancer.