Dimethylsilane polyamines: cytostatic compounds with potentials as anticancer drugs.
Several dimethylsilane tetramines [homologs of spermine with an Si(CH3)2 group in the central carbon chain], a carbon analog of the dimethylsilane tetramines [containing C(CH3)2 instead of Si(CH3)2] and a dimethylsilane hexamine were studied with regard to their cytotoxic activity and their ability to interact with double-stranded DNA. All polyamine analogs exerted cytostatic effects to several cell lines at micromolar concentrations. Their ability to condense DNA was comparable to and their ability to displace ethidium bromide from binding to DNA was superior to that of spermine. Their cytostatic effect was not correlated with the depletion of cellular spermidine concentrations. It is suggested that the new polyamine analogs act mainly by displacing spermidine from binding sites which are essential for the promotion of cell growth.
Douaud
F
F
UPRES-A CNRS 6027, Institut de Recherche Contre le Cancer, Faculté de Médecine, Université de Rennes I, France.
Le Roch
N
N
Renault
J
J
Havouis
R
R
Vaultier
M
M
Moulinoux
J P
JP
Seiler
N
N
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016466:CHO Cells / Q000187:drug effects / Q000378:metabolism; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000378:metabolism; D006224:Cricetinae; D004247:DNA / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D000518:Eflornithine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007939:Leukemia L1210 / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D011073:Polyamines / Q000737:chemistry / Q000494:pharmacology*; D011700:Putrescine / Q000037:antagonists & inhibitors / Q000378:metabolism; D012821:Silanes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013095:Spermidine / Q000037:antagonists & inhibitors / Q000378:metabolism
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011073:Polyamines; D012821:Silanes; D004247:DNA; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine