title: Isatin Derived Spirocyclic Analogues with α-Methylene-γ-butyrolactone as Anticancer Agents: A Structure-Activity Relationship Study.
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.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Rana
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Blowers
authors.affiliation: Division of Gynecology Oncology, Department of Women's Health and Josephine Ford Cancer Center, Henry Ford Hospital , Detroit, Michigan 48202, United States.
authors.forename: Calvin
authors.initials: C
authors.lastname: Tebbe
authors.forename: Jacob I
authors.initials: JI
authors.lastname: Contreras
authors.forename: Prakash
authors.initials: P
authors.lastname: Radhakrishnan
authors.forename: Smitha
authors.initials: S
authors.lastname: Kizhake
authors.forename: Tian
authors.initials: T
authors.lastname: Zhou
authors.forename: Rajkumar N
authors.initials: RN
authors.lastname: Rajule
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Arnst
authors.affiliation: Division of Gynecology Oncology, Department of Women's Health and Josephine Ford Cancer Center, Henry Ford Hospital , Detroit, Michigan 48202, United States.
authors.forename: Adnan R
authors.initials: AR
authors.lastname: Munkarah
authors.affiliation: Division of Gynecology Oncology, Department of Women's Health and Josephine Ford Cancer Center, Henry Ford Hospital , Detroit, Michigan 48202, United States.
authors.forename: Ramandeep
authors.initials: R
authors.lastname: Rattan
authors.forename: Amarnath
authors.initials: A
authors.lastname: Natarajan
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007510:Isatin / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D013141:Spiro Compounds; D014409:Tumor Necrosis Factor-alpha; D007510:Isatin