Synthesis and anticancer activity of novel spiro-isoxazoline and spiro-isoxazolidine derivatives of α-santonin

Eur J Med Chem. 2013 May:63:279-89. doi: 10.1016/j.ejmech.2013.01.003.

Jabeena Khazir ¹, 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

Affiliations

Affiliation

1 Medicinal Chemistry Division, Indian Institute of Integrative Medicine, Jammu 180001, India.

PMID: 23501113 DOI: 10.1016/j.ejmech.2013.01.003

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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