Inhibition of pig kidney diamine oxidase by nazlinin and nazlinin derivatives.
Nazlinin (1-(4-butylamino)-1,2,3,4-tetrahydro-beta-carboline) (1), an alkaloid recently isolated from Nitraria schoberi, and its two derivatives, 1-(4-butylamino)-3,4-dihydro-beta-carboline (2) and 1-(4-butylamino)-beta-carboline (3), were synthesized and their interaction with pig kidney diamine oxidase (PKDO) was studied. Nazlinin appeared to be a very poor substrate while 3 was a good substrate with an apparent Km of 9.3-10(-5) M. The enzyme was inhibited by 1 and 2. With both compounds the mode of inhibition found was non-competitive and inhibition constants calculated from the slopes and intercepts of double-reciprocal plots show that 2 is a much more potent inhibitor than the natural product. The relationship between the structure of these compounds and the results found is discussed.
Laboratory of Organic Chemistry, University of Amsterdam, The Netherlands.
E
E
Cheng
H L
HL
Dekker
B F
BF
van Gelder
G J
GJ
Koomen
D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D002243:Carbolines / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D013552:Swine
C097174:1-(4-aminobutyl)-3,4-dihydro-beta-carboline; C097175:1-(4-aminobutyl)-beta-carboline; D002243:Carbolines; D004791:Enzyme Inhibitors; C073065:nazlinine; D006631:Amine Oxidase (Copper-Containing)