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. doi: 10.1021/acs.jmedchem.6b00400.

Sandeep Rana, Elizabeth C Blowers, Calvin Tebbe ¹, Jacob I Contreras, Prakash Radhakrishnan, Smitha Kizhake, Tian Zhou, Rajkumar N Rajule, Jamie L Arnst, Adnan R Munkarah ¹, Ramandeep Rattan ¹, Amarnath Natarajan

Affiliations

Affiliation

1 Division of Gynecology Oncology, Department of Women's Health and Josephine Ford Cancer Center, Henry Ford Hospital , Detroit, Michigan 48202, United States.

PMID: 27077228 DOI: 10.1021/acs.jmedchem.6b00400

Abstract

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.

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