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

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• 作者：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
• 刊名：Journal of Medicinal Chemistry
• 出版年：2016
• 出版时间：May 26, 2016
• 年：2016
• 卷：59
• 期：10
• 页码：5121-5127
• 全文大小：418K
• 年卷期：0
• ISSN：1520-4804

文摘

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.