title: Synthesis and anticancer activity of novel spiro-isoxazoline and spiro-isoxazolidine derivatives of α-santonin.
abstract: In the present study, novel spiro derivatives of α-santonin were prepared and tested for their anticancer activity against a panel of six human cancer cell lines. Spiro-isoxazoline and spiro-isoxazolidine derivatives have been generated on C-ring of α-santonin (α-methylene-γ-butyrolactone) by the 1,3-dipolar cycloaddition of α-santonin derivative 6 with nitrile oxides 7 and nitrones 9 respectively. Among all, compound 10b″ had shown IC50 of 0.01, 0.5 and 0.3 μM against PC-3, THP-1 and MCF-7 cell lines respectively. Further, flow cytometry studies showed that PC-3 cells treated with the spiro-isoxazolidine derivative 10b″ were arrested in the sub G1 phase of the cell cycle in a concentration dependent manner. The spiro-isoxazolidine derivative 10b″ also showed concentration dependent inhibitory activity against NF-κB, p65 with 57% inhibition in 24 h at 10 μM.
authors.affiliation: Medicinal Chemistry Division, Indian Institute of Integrative Medicine, Jammu 180001, India.
authors.forename: Jabeena
authors.initials: J
authors.lastname: Khazir
authors.forename: Parvinder Pal
authors.initials: PP
authors.lastname: Singh
authors.forename: D Mahendhar
authors.initials: DM
authors.lastname: Reddy
authors.forename: Irfan
authors.initials: I
authors.lastname: Hyder
authors.forename: Syed
authors.initials: S
authors.lastname: Shafi
authors.forename: S D
authors.initials: SD
authors.lastname: Sawant
authors.forename: Gousia
authors.initials: G
authors.lastname: Chashoo
authors.forename: Ajay
authors.initials: A
authors.lastname: Mahajan
authors.forename: M S
authors.initials: MS
authors.lastname: Alam
authors.forename: A K
authors.initials: AK
authors.lastname: Saxena
authors.forename: S
authors.initials: S
authors.lastname: Arvinda
authors.forename: B D
authors.initials: BD
authors.lastname: Gupta
authors.forename: H M Sampath
authors.initials: HM
authors.lastname: Kumar
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D061986:MCF-7 Cells; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D012500:Santonin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D007555:Isoxazoles; D051996:Transcription Factor RelA; D012500:Santonin