2-Oxy-3-phenylacrylic Acid Derivatives As Potent Mcl-1 Inhibitors for Treatment of Cancer

Myeloid cell leukemia-1 (Mcl-1) is a crucial member of Bcl-2 family protein and is recognized as a promising therapeutic target for cancer treatment. Here, based on the lead compound we reported earlier, a focused library of analogues was designed, synthesized and evaluated for the inhibitory activity against Mcl-1. 2-oxy-3-phenylacrylic acid derivative III-2, turned out to be the most potent compound with good binding affinity for Mcl-1 and anti-proliferative activities. In addition, the effective inhibition of cell migration, the improvement of apoptosis and the decreased expression of Mcl-1 by compound III-2, as well as the molecule docking elucidated its mechanism of action. Taken together, 2-oxy-3-phenylacrylic acid derivatives may represent a new class of Mcl-1 inhibitors and deserve further study.