Histone deacetylases (HDACs) inhibitors have multiple effects targeting the
cancer cells and have become one of the promising cancer therapeutics with possibly
broad applicability. Combination of HDAC inhibitors with the cytotoxic fluorouracil
(5-FU) showed additive and synergistic effects both in vitro and in vivo. To explore
the possibility in cancer therapy of a bivalent agent that combines two bioactive
groups within a single molecular architecture, we designed and synthesized
new dual-acting compounds by combining the bioactive fragment of MS-275, a clinical
HDACs inhibitor, with cytotoxic agent 5-FU. The target compounds 9a and 9b
showed comparable HDACs inhibition with MS-275 and moderate antiproliferative
acitivities against six cancer cells lines.
Keywords: Anticancer, HDAC, MS-275, Multitarget, 5-Fluorouracil.
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