First synthesis and biological evaluation of novel spin-labeled derivatives of deoxypodophyllotoxin

Deoxypodophyllotoxin inhibits tubulin polymerization and induces cell cycle arrest at G2/M, followed by apoptosis. In order to find compounds with superior bioactivity and less toxicity, a series of spin-labeled derivatives of deoxypodophyllotoxin were synthesized by reacting 4′-demethyl-4-deoxypodophyllotoxin (DPPT) with N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyloxycarbonyl) amino acids. The cytotoxic activities against three tumor cell lines (HL-60, RPMI-8226, A-549) in vitro and the antioxidative activities in tissues of Sprague Dawley (SD) rats of target compounds were evaluated, and the results indicated that compounds 11a–h were more potent in terms of cytotoxicities and antioxidative activities than either parent compound DPPT or anticancer drug VP-16.

The spin-labeled derivatives of deoxypodophyllotoxin 11a–h showed higher potent cytotoxicities (HL-60, RPMI-8226 and A-549) and antioxidative activities than parent compound DPPT and anticancer drug VP-16.Figure optionsDownload as PowerPoint slide