Isatin Derived Spirocyclic Analogues with α-Methylene-γ-butyrolactone as Anticancer Agents: A Structure-Activity Relationship Study.
Rana S, Blowers EC, Tebbe C, Contreras JI, Radhakrishnan P, Kizhake S, Zhou T, Rajule RN, Arnst JL, Munkarah AR, Rattan R, Natarajan A. Isatin Derived Spirocyclic Analogues with α-Methylene-γ-butyrolactone as Anticancer Agents: A Structure-Activity Relationship Study. J Med Chem. 2016 May 26;59(10):5121-7.
Journal of medicinal chemistry
Design, synthesis, and evaluation of α-methylene-γ-butyrolactone analogues and their evaluation as anticancer agents is described. SAR identified a spirocyclic analogue 19 that inhibited TNFα-induced NF-κB 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-μM potency. Our data suggest that an isatin-derived spirocyclic α-methylene-γ-butyrolactone is a suitable core for optimization to identify novel anticancer agents.
Medical Subject Headings
Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Isatin; Molecular Structure; NF-kappa B; Spiro Compounds; Structure-Activity Relationship; Tumor Necrosis Factor-alpha