Design and Synthesis of an Hsp90 and HDAC Dual Inhibitor as Antitumor Agent

BackgroundCancer incidence and mortality have been increasing, and cancer is still the leading cause of death all over the world. Therefore, expanding the arsenal of anticancer drugs with high efficiency and low toxicity is still one of the most challenging tasks. As a branch of antitumor drug design and discovery, dual-targeting drug candidates draw extensive attention.ObjectiveIn this work, we try to construct a multitarget drug candidate and evaluate its antitumor effects.MethodsHsp90 and histone deacetylase were selected as two targets to design a dual targeting inhibitor w11. Enzyme inhibition work, cell viability assay, and docking simulation were carried out to evaluate the activity of the compound.Resultsw11 could inhibit the activity of Hsp90a and HDAC6 with the IC50 of 50.1 nM and 8.1 nM, respectively. In cell viability assay, five human tumor cell lines Eca-109, FaDu, HN6, MCF-7 and MDA-MB-231 were used, results showed that w11 could potently inhibit the proliferation of three human lines with IC50 values in the nM range. Molecular docking experiments proved the rationality of structure design.ConclusionCompound w11 was a potent Hsp90 and HDAC dual inhibitor for anticancer research.