Design, synthesis, and biological evaluation of novel spin-labeled derivatives of podophyllotoxin as potential antineoplastic agents. Part XII

Abstract

Five novel nitroxyl spin-labeled ester derivatives of podophyllotoxin (11a–11e) have been prepared and their structural information on these nitroxyl spin-labeled ester derivatives of podophyllotoxin (11a–11e) using ¹HNMR spectroscopy was efficiently obtained by application of the in situ reduction of representative nitroxyl spin-labeled ester derivative of podophyllotoxin 11e with phenylhydrazine for the preparation of N-hydroxylamine 12 in the NMR tube. These novel derivatives were further evaluated for their in vitro cytotoxic activity against five neoplastic cell lines (K562, HL-60, SPCA-1, Lewis, and L-1210) using MTT assay. Most of the target compounds (except for all these compounds against SPCA-1) exhibited more pronounced cytotoxicity against several neoplastic cell lines than that of the prototypical inhibitor etoposide.

¶For part XI, see Jin, Y., Chen, S. W., and Tian, X. Bioorg. Med. Chem. 2006, 14, 3062-3068.

Keywords:

• Podophyllotoxin derivatives
• Antineoplastic properties
• Spin-labeled

Acknowledgement

This work was financially supported by the Natural Science Foundation of Gansu Province specially foundation (ZGS-033-A-43-013).

Notes

¶For part XI, see Jin, Y., Chen, S. W., and Tian, X. Bioorg. Med. Chem. 2006, 14, 3062-3068.