Anticancer drugs. II. Synthesis and biological evaluation of spin labeled derivatives of podophyllotoxin.

Abstract

The spin labeled derivatives of podophyllotoxin, 4-[4''-(2'',2'',6'',6''-tetramethyl-l''-piperidinyloxy)amino] -4'-demethylepipodophyllotoxin(GP-7,3) and N-podophyllic acid-N''-[4-(2,2,6,6-tetramethyl-l-piperidinyloxy)] thiosemicarbazide(GP-4,5) were synthesized and tested for their anticancer activity against the mouse solid tumors S180 and HepA in vivo, and the mouse lymphocytic leukemia L1210 and human stomach carcinoma SGC-7901 cells in vitro. At equitoxic concentrations, the anticancer activity of GP-7(3) was found to be similar to that of the clinically used VP-16(2). The toxicity of GP-7(3) (LD50231.2 mg/Kg) is 3.3 times lower than that of VP-16 (LD50 69.5 mg/Kg). GP-7(3) exhibits low subchronic toxicity. The total chemical yield of GP-7 (26%) is 4 times higher than that of VP-16 (6%) (based on podophyllotoxin). Therefore, GP-7(3) seems to be a promising new entry into the podophyllotoxin class of anticancer drugs.

• Authors: Y Z Chen, Y G Wang, J X Li, X Tian, Z P Jia, P Y Zhang
• Journal: Life sciences (Life Sci) Vol. 45 Issue 26 Pg. 2569-75 ( 1989) ISSN: 0024-3205 [Print] Netherlands
• PMID: 2615556 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Spin Labels
• Podophyllotoxin

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, toxicity)
• Drug Screening Assays, Antitumor
• Female
• Humans
• Lethal Dose 50
• Male
• Mice
• Molecular Structure
• Neoplasms, Experimental (drug therapy)
• Organ Size
• Podophyllotoxin (analogs & derivatives, pharmacology, toxicity)
• Spin Labels
• Tumor Cells, Cultured