Design, synthesis, and biological activity evaluation of new tankyrase-2 directed inhibitors.

A new series of flavonoids and quinolone derivatives were designed, synthesized and, evaluated for their biological activity. Among them, compound 14e showed better inhibition potency against TNKS2 in comparison with G007-LK, one of the most potent preclinical stage TNKS inhibitor. Molecular docking results showed that 14e occupied both the adenosine and nicotinamide pockets and formed a hydrogen bond with Met1054 of TNKS2. This study provides a lead for the design and discovery of potent and selective TNKS2 inhibitors.