Design, synthesis and antiproliferative activities of novel benzamides derivatives as HDAC inhibitors

• Novel benzamides derivatives were synthesized and evaluated their antitumor activities against three human cancer cell lines.
• All compounds demonstrated more or similar potent activities in comparison with MS-275.
• Most compounds exhibited a reasonable inhibitory potency against HDAC1.
• Compound 4a could be considered as a candidate HDAC inhibitor for further development.

Guided by the principle of nonclassical electronic isosterism and structural optimization, a series of novel HDAC inhibitors bearing a bicyclic heterocycle moiety were designed and synthesized based on the lead compound of MS-275. All the prepared compounds were evaluated for their in vitro antiproliferative activities against HCT-116, MCF-7 and A549 human cancer cell lines, all compounds exerted excellent antitumor activities. Moreover, the compound 4a exhibited an acceptable pharmacokinetic profile with bio-availability in rat of 76% and could be considered as a candidate compound for further development.

A series of benzamides derivatives were designed and synthesized as highly potent HDAC inhibitors based on the lead compound of MS-275.Figure optionsDownload as PowerPoint slide