Tubulin/HDAC dual-target inhibitors: Insights from design strategies, SARs, and therapeutic potential

Microtubules, one of the cytoskeletons in eukaryotic cells, maintain the proper operation of several cellular functions. Additionally, they are regulated by the acetylation of HDAC6 and SIRT2 which affects microtubule dynamics. Given the fact that tubulin and HDAC inhibitors play a synergistic effect in the treatment of many cancers, the development of tubulin/HDAC dual-target inhibitors is conducive to addressing multiple limitations including drug resistance, dose toxicity, and unpredictable pharmacokinetic properties. At present, tubulin/HDAC dual-target inhibitors have been obtained in three main ways: uncleavable linked pharmacophores, cleavable linked pharmacophores, and modification of single-target drugs. Their therapeutic efficacy has been verified in vivo and in vitro assays. In this article, we reviewed the research progress of tubulin/HDAC dual inhibitors from design strategies, SARs, and biological activities, which may provide help for the discovery of novel tubulin/HDAC dual inhibitors. [Display omitted] •Tubulin and HDAC affect the development of eukaryotic cells in various ways and are currently attractive directions in anti-cancer therapy.•Combined inhibition of tubulin and HDAC exerts synergistic effects in slowing the development of variety tumor cells.•Structural modification strategies of dual inhibitors are summarized, and some suggestions are proposed for the design direction of dual inhibitors in the future.