Title

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

Document Type

Article

Publication Date

5-26-2016

Publication Title

Journal of medicinal chemistry

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.

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

PubMed ID

27077228

Volume

59

Issue

10

First Page

5121

Last Page

5127

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