Synthesis and biological evaluation of N-aryl salicylamides with a hydroxamic acid moiety at 5-position as novel HDAC–EGFR dual inhibitors

A novel series of N-aryl salicylamides with a hydroxamic acid moiety at 5-position were synthesized efficiently. Their activities against EGFR kinase and HDACs were evaluated. All compounds displayed inhibitory activity against EGFR and HDACs. The antiproliferative activities of synthesized compounds were evaluated by MTT method against human cancer cell lines A431, A549 and HL-60. Compound 1o showed the most potent inhibitory activity against A431 and A549. Compounds 1k and 1n exhibited higher potency against HL-60 than gefitinib and SAHA. N-Aryl salicylamides with a hydroxamic acid moiety at 5-position is another new HDAC–EGFR dual inhibitors.

N-Aryl salicylamide and the pharmacophore of HDAC inhibitor (hydroxamic acid) were incorporated to present a novel class of EGFR–HDAC dual inhibitors.Figure optionsDownload as PowerPoint slide