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.
Cheng
E
E
Laboratory of Organic Chemistry, University of Amsterdam, The Netherlands.
Dekker
H L
HL
van Gelder
B F
BF
Koomen
G J
GJ
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)