title: (2R,5R)-6-heptyne-2,5-diamine, an extremely potent inhibitor of mammalian ornithine decarboxylase.
abstract: It was previously shown that 5-hexyne-1,4-diamine is a potent enzyme-activated irreversible inhibitor of mammalian ornithine decarboxylase. However this compound has secondary pharmacological effects owing to its in vivo oxidation to 4-aminohex-5-ynoic acid, an irreversible inhibitor of 4-aminobutyrate aminotransferase. The first step of this oxidation is catalysed by mitochondrial monamine oxidase. The monomethyl and dimethyl analogues of 5-hexyne-1,4-diamine, i.e. 6-heptyne-2,5-diamine and 2-methyl-6-heptyne-2,5-diamine, which cannot be substrate of monoamine oxidase, were tested as selective irreversible inhibitors of ornithine decarboxylase. Our results demonstrate that (2R,5R)-6-heptyne-2,5-diamine is greater than 10 times more potent, both in vitro and in vivo, than alpha-difluoromethylornithine, the most widely used irreversible inhibitor of this enzyme.
mesh_terms: D000480:Alkynes; D000818:Animals; D003959:Diamines / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D008297:Male; D065108:Ornithine Decarboxylase Inhibitors; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000480:Alkynes; D003959:Diamines; D065108:Ornithine Decarboxylase Inhibitors; C039613:6-heptyne-2,5-diamine