Synthesis, cytotoxicity and apoptosis of naphthalimide polyamine conjugates as antitumor agents.
Several naphthalimide polyamine conjugates were synthesized and evaluated for in vitro cytotoxicity against human leukemia K562, murine melanoma B16, Chinese hamster ovary CHO cell lines. Both triamine moieties and the length of spacers were crucial in elevating the potency of 1,8-naphthalimide. The typical compounds 5a and 5d exhibited excellent cell selectivity to cancer cells through the human hepatoma BEL-7402 and human normal hepatocyte QSG-7701 screens. In addition, 5d could disturb the cell cycle in B16 cells. The research on caspase activity and cytochrome c indicated that 5d could induce B16 cell apoptosis via both the mitochondrial and membrane death receptor pathways, and the Bcl-2 family numbers were involved in the control of apoptosis.
Tian
Zhi-yong
ZY
Institute of Natural Products and Medicinal Chemistry, Henan University, Kaifeng 475001, China; Pharmacy College, Tianjin University, Tianjin 300072, China.
Xie
Song-qiang
SQ
Du
Yao-wu
YW
Ma
Yuan-fang
YF
Zhao
Jin
J
Gao
Wen-yuan
WY
Wang
Chao-jie
CJ
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D045304:Cytochromes c / Q000187:drug effects; D006801:Humans; D051379:Mice; D053644:Naphthalimides / Q000138:chemical synthesis* / Q000494:pharmacology; D011073:Polyamines / Q000138:chemical synthesis* / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D061945:Caspase Inhibitors; D053644:Naphthalimides; D011073:Polyamines; D019253:Proto-Oncogene Proteins c-bcl-2; D045304:Cytochromes c