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

Abstract Purpose 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. Methods The in vitro antiproliferative efficacies of compound B8HA against MDA-MB-231, MDA-MB-468, MCF-7, 4T1, A549, HCT-116, HT-29 and K562 were evaluated with MTT assay. Moreover, the potencies of B8HA as inhibitors of HDAC and tubulin polymerase were also evaluated in vitro and vivo. Results Comparing to the classical HDACi SAHA, B8HA has higher potency to induce apoptosis and inhibits the migratory and invasive abilities of tumor cells under the same dose in vitro and vivo. B8HA as tubulin inhibition is also able to inhibit the formation of capillary-like structures as well as to disrupt existing tubules. Conclusion These results indicated that compound B8HA is a potent inhibitor of both HDAC and tubulin, leading to excellent in vitro and in vivo antiproliferative activities.