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.
Zhang
Zhi-Wei
ZW
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China.
Zhang
Jia-Qiang
JQ
Hui
Ling
L
Chen
Shi-Wu
SW
Tian
Xuan
X
D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004365:Drugs, Chinese Herbal; D006801:Humans; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D013113:Spin Labels
D000975:Antioxidants; D004365:Drugs, Chinese Herbal; D013113:Spin Labels; C014451:deoxypodophyllotoxin; D011034:Podophyllotoxin