Synthesis, biological evaluation and DNA binding properties of novel bleomycin analogues.
A series of bleomycin analogues was prepared with a facile synthetic method. All the compounds were shown to display significant antitumor activity against HeLa and BGC-823 cell lines in vitro. The binding properties with CT-DNA and cleavage efficiency to pBR322 DNA were investigated, the results indicate that there is a positive relationship between DNA cleavage efficiency and the binding affinity to DNA, and the antitumor activity of the bleomycin analogues is enhanced as the hydrophobicity of the C-terminus substituent side chain increased.
Xu
Zhi-Dong
ZD
National Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100083, Peoples Republic of China.
Wang
Min
M
Xiao
Su-Long
SL
Liu
Chun-Li
CL
Yang
Ming
M
D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D001761:Bleomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002847:Chromatography, Agarose; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013778:Tetrazolium Salts; D013844:Thiazoles
D000903:Antibiotics, Antineoplastic; D004273:DNA, Neoplasm; D013778:Tetrazolium Salts; D013844:Thiazoles; D001761:Bleomycin; C022616:thiazolyl blue