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.
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Authors | Jabeena Khazir, Parvinder Pal Singh, D Mahendhar Reddy, Irfan Hyder, Syed Shafi, S D Sawant, Gousia Chashoo, Ajay Mahajan, M S Alam, A K Saxena, S Arvinda, B D Gupta, H M Sampath Kumar |
Journal | European journal of medicinal chemistry
(Eur J Med Chem)
Vol. 63
Pg. 279-89
(May 2013)
ISSN: 1768-3254 [Electronic] France |
PMID | 23501113
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2013 Elsevier Masson SAS. All rights reserved. |
Chemical References |
- Antineoplastic Agents
- Isoxazoles
- Transcription Factor RelA
- Santonin
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Topics |
- Antineoplastic Agents
(chemical synthesis, chemistry, pharmacology)
- Cell Cycle Checkpoints
(drug effects)
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Crystallography, X-Ray
- Dose-Response Relationship, Drug
- Drug Screening Assays, Antitumor
- Flow Cytometry
- G1 Phase
(drug effects)
- Humans
- Inhibitory Concentration 50
- Isoxazoles
(chemical synthesis, chemistry, pharmacology)
- MCF-7 Cells
- Models, Chemical
- Molecular Conformation
- Molecular Structure
- Santonin
(chemical synthesis, chemistry, pharmacology)
- Stereoisomerism
- Transcription Factor RelA
(antagonists & inhibitors, metabolism)
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