Synthesis, mutagenicity, binding to pBR 322 DNA and antitumour activity of platinum(II) complexes with ethambutol.
Platinum complexes with N,N'-bis(1-hydroxybut-2-yl)ethylenediamine, [PtCl2(ethambutol)] were prepared and the biological activity of three isomers [with (-), (+) and (+/-) ethambutol, respectively] investigated. All species interact with the Bam HI and Ava I recognition sequences showing a binding preference for GC rich sequences of DNA. The complex which showed the greatest interaction with adjacent guanines, [PtCl2[+/-)ethambutol)] was also found to be the most mutagenic of the three. On the other hand, only [PtCl2[+)ethambutol)] had a considerable antitumour activity against both P388 leukaemia and Lewis lung carcinoma, and this was not correlated either with restriction enzyme blocking activity or with mutagenicity.
Coluccia
M
M
Istituto di Patologia Generale, Bari, Italy.
Fanizzi
F P
FP
Giannini
G
G
Giordano
D
D
Intini
F P
FP
Lacidogna
G
G
Loseto
F
F
Mariggio
M A
MA
Nassi
A
A
Natile
G
G
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001665:Binding Sites; D002945:Cisplatin / Q000494:pharmacology*; D004977:Ethambutol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D007941:Leukemia P388 / Q000188:drug therapy*; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology*; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D010957:Plasmids; D015183:Restriction Mapping; D012486:Salmonella typhimurium / Q000187:drug effects
D000970:Antineoplastic Agents; D009153:Mutagens; D009944:Organoplatinum Compounds; C068424:platinum-ethambutol; D004977:Ethambutol; D002945:Cisplatin