Bis(7-amino-4-azaheptyl)dimethylsilane: a new tetramine with polyamine-like features. Effects on cell growth.
Bis(7-amino-4-azaheptyl)dimethylsilane is a new type of aliphatic polycation with structural features resembling those of spermine. The elongation to a seven-membered carbon chain in which the central CH2-group was substituted by (CH3)2Si renders the molecule more lipophilic than spermine. Cells accumulate the compound via the polyamine transport system. Due to suppression of ornithine decarboxylase, de novo putrescine biosynthesis is impaired, and intracellular putrescine and spermidine concentrations are depleted. Depletion of intracellular spermidine together with binding to functionally important polyamine binding sites are considered the main features of the compound which cause cytostatic, and at high concentrations, cytotoxic effects.
Delcros
J G
JG
URA CNRS 1529, Institut de Recherche Contre le Cancer, Faculté de Médecine, Rennes, France.
Vaultier
M
M
Le Roch
N
N
Havouis
R
R
Moulinoux
J P
JP
Seiler
N
N
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000187:drug effects; D011073:Polyamines / Q000378:metabolism*; D011700:Putrescine / Q000378:metabolism; D012821:Silanes / Q000378:metabolism / Q000627:therapeutic use*; D013095:Spermidine / Q000378:metabolism
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D011073:Polyamines; D012821:Silanes; C103070:bis(7-amino-4-azaheptyl)dimethylsilane; D009955:Ornithine Decarboxylase; D013095:Spermidine; D011700:Putrescine