Inactivation of bovine plasma amine oxidase by haloallylamines.
Various 2- and 3-haloallylamines were synthesized and evaluated as inhibitors of the quinone-dependent bovine plasma amine oxidase (BPAO). 3-Haloallylamines, which were previously found to be good inhibitors of the flavin-dependent mitochondrial monoamine oxidase (MAO), exhibited a time-dependent inactivation of BPAO, with the 2-phenyl analogs being more potent than the 2-methyl analogs. No plateau of enzyme activity loss was observed, suggestive of a lack of competitive partitioning to normal turnover. The (E)- and (Z)-2-phenyl-3-fluoro analogs were the most potent (low microM IC(50)s), with the corresponding 3-bromo and 3-chloro analogs being >10-fold less potent. In each case, the Z-isomers were more potent than the E-isomers, the reverse of the configurational inhibitory preference observed with MAO. In contrast to the 2-phenyl analogs, 3-phenyl-2(or 3)-chloroallylamines displayed a partitioning behavior, consistent with these being both substrates and inactivators of BPAO.
Kim
Jisook
J
Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106, USA.
Zhang
Yuming
Y
Ran
Chongzhao
C
Sayre
Lawrence M
LM
D000499:Allylamine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors* / Q000097:blood; D000818:Animals; D016227:Benzoquinones / Q000737:chemistry; D002417:Cattle; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006219:Halogens / Q000737:chemistry; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008956:Models, Chemical
D016227:Benzoquinones; D004791:Enzyme Inhibitors; D006219:Halogens; C004532:quinone; D000499:Allylamine; D006631:Amine Oxidase (Copper-Containing)