Anticancer drugs. II. Synthesis and biological evaluation of spin labeled derivatives of podophyllotoxin.
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.
Chen
Y Z
YZ
Department of Chemistry, Lanzhou University, People's Republic of China.
Wang
Y G
YG
Li
J X
JX
Tian
X
X
Jia
Z P
ZP
Zhang
P Y
PY
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009929:Organ Size; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D013113:Spin Labels; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D013113:Spin Labels; D011034:Podophyllotoxin