Anticancer drugs. II. Synthesis and biological evaluation of spin labeled derivatives of podophyllotoxin |
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| Authors: | Y Z Chen Y G Wang J X Li X Tian Z P Jia P Y Zhang |
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| Affiliation: | Department of Chemistry, Lanzhou University, People's Republic of China. |
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| 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. |
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