The design, synthesis, and evaluation of the biological activity of hydroxamic derivatives of sorafenib

Sorafenib is a multiple tyrosine kinase inhibitor that is used in the treatment of liver and renal cancers. We synthesized the hydroxamic derivatives of sorafenib bearing the pharmacophore elements of zinc-dependent histone deacetylase inhibitors. We uncovered that suppression of cancer cell proliferation by the synthesized hybrid inhibitors critically depends on the structure of the "deacetylase" element.