Inhibition of bovine plasma amine oxidase by 1,4-diamino-2-butenes and -2-butynes.
Bovine plasma amine oxidase (BPAO) was previously shown to be irreversibly inhibited by propargylamine and 2-chloroallylamine. 1,4-Diamine versions of these two compounds are here shown to be highly potent inactivators, with IC50 values near 20 microM. Mono-N-alkylation or N,N-dialkylation greatly lowered the inactivation potency in every case, whereas the mono-N-acyl derivatives were also weaker inhibitors and enzyme activity was recoverable. The finding that the bis-primary amines 1,4-diamino-2-butyne (a known potent inhibitor of diamine oxidases) and Z-2-chloro-1,4-diamino-2-butene are potent inactivators of BPAO is suggestive of unexpected similarities between plasma amine oxidase and the diamine oxidases and implies that it may be unwise to attempt to develop selective inhibitors of diamine oxidase using a diamine construct.
Jeon
Heung-Bae
HB
Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106, USA.
Lee
Younghee
Y
Qiao
Chunhua
C
Huang
He
H
Sayre
Lawrence M
LM
D000478:Alkylation; D000499:Allylamine / Q000494:pharmacology; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D003959:Diamines / Q000737:chemistry* / Q000494:pharmacology*; D004789:Enzyme Activation; D007928:Lethal Dose 50; D011700:Putrescine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013997:Time Factors
D003959:Diamines; C021006:diaminobutene; D000499:Allylamine; C063335:1,4-diamino-2-butyne; D006631:Amine Oxidase (Copper-Containing); D011700:Putrescine