Synthesis and evaluation of unsymmetrical polyamine derivatives as antitumor agents.
A series of unsymmetrically substituted polyamine derivatives were prepared and their cytotoxicities in mouse leukemia L1210, melanoma B16, and HeLa cells were investigated. The in vitro cytotoxicity revealed that these conjugates could recognize the polyamine transporter, and the N-ethyl modified homospermidine moiety may be another efficient carrier as homospermidine even though the introduction of terminal alkyl groups led to reduced cytotoxicity in comparison with the un-substituted counterpart 1. The ornithine decarboxylase and topoisomerase II inhibition experiments indicated that ODC and TOPO II were potential, but not unique targets of these conjugates. Furthermore, the in vivo antitumor activities illustrated that the representative conjugate 2f and the homospermidine analogue 1 evidently inhibited the tumor growth and significantly increased the survival time of mice-bearing sarcoma 180 cells.
Institute of Natural Products & Medicinal Chemistry, Henan University, Henan, Kaifeng 475001, China.
Jianhong
J
Wang
Songqiang
S
Xie
Yanjie
Y
Li
Yongjun
Y
Guo
Yuanfang
Y
Ma
Jin
J
Zhao
Otto
O
Phanstiel
Chaojie
C
Wang
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013095:Spermidine / Q000494:pharmacology; D015996:Survival Rate; D059005:Topoisomerase II Inhibitors
D000970:Antineoplastic Agents; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D059005:Topoisomerase II Inhibitors; D013095:Spermidine