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

ABSTRACT: Design, synthesis, and evaluation of ?-methylene-?-butyrolactone analogues and their evaluation as anticancer agents is described. SAR identified a spirocyclic analogue 19 that inhibited TNF?-induced NF-?B 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-?M potency. Our data suggest that an isatin-derived spirocyclic ?-methylene-?-butyrolactone is a suitable core for optimization to identify novel anticancer agents.

SUBMITTER: Rana S

PROVIDER: S-EPMC5273401 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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

Rana Sandeep S Blowers Elizabeth C EC Tebbe Calvin C Contreras Jacob I JI Radhakrishnan Prakash P Kizhake Smitha S Zhou Tian T Rajule Rajkumar N RN Arnst Jamie L JL Munkarah Adnan R AR Rattan Ramandeep R Natarajan Amarnath A

Journal of medicinal chemistry 20160426 10

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 o ...[more]

PMID: 27077228

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