Isatin Derived Spirocyclic Analogues with α-Methylene-γ-butyrolactone as Anticancer Agents: A Structure-Activity Relationship Study

Design, synthesis, and evaluation of alpha-methylene-gamma-butyrolactone analogues and their evaluation as anticancer agents is described. SAR identified a spirocyclic analogue 19 that inhibited TNF alpha-induced NF-kappa B activity, cancer cell growth and tumor growth in an ovarian cancer model. A second iteration of synthesis and screening identified 29 which inhibited cancer cell growth with low-mu M potency. Our data suggest that an isatin-derived spirocyclic alpha-methylene-gamma-butyrolactone is a suitable core for optimization to identify novel anticancer agents.