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

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

Research output: Contribution to journalArticle

42 Scopus citations

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-ΰB 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-ÎM potency. Our data suggest that an isatin-derived spirocyclic α-methylene-γ-butyrolactone is a suitable core for optimization to identify novel anticancer agents.

Original languageEnglish (US)
Pages (from-to)5121-5127
Number of pages7
JournalJournal of Medicinal Chemistry
Volume59
Issue number10
DOIs
StatePublished - May 26 2016

    Fingerprint

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Rana, S., Blowers, E. C., Tebbe, C., Contreras, J. I., Radhakrishnan, P., Kizhake, S., Zhou, T., Rajule, R. N., Arnst, J. L., Munkarah, A. R., Rattan, R., & Natarajan, A. (2016). Isatin Derived Spirocyclic Analogues with α-Methylene-γ-butyrolactone as Anticancer Agents: A Structure-Activity Relationship Study. Journal of Medicinal Chemistry, 59(10), 5121-5127. https://doi.org/10.1021/acs.jmedchem.6b00400