Interaction of rat lung SSAO with the novel 1-N-substituted thiocarbamoyl-3-substituted phenyl-5-(2-pyrolyl)-2-pyrazoline derivatives.
Interactions of twelve new synthesized 1-N-substituted thiocarbamoyl-3-substituted phenyl-5-pyrolyl-2-pyrazoline derivatives with rat lung semicarbazide-sensitive amine oxidase (SSAO) were assessed. Pyrazoline derivatives were synthesized according to previous methods and SSAO was purified from the crude microsomal fractions of rat lung.Three compounds (3e, 3f, 3k) with a p-methoxy group at the phenyl ring inhibited rat lung SSAO non-competitively and irreversibly, and showed higher affinity towards SSAO when expressed in terms of IC(50) for SSAO/Monoamine oxidase B (MAO-B). Since these novel pyrazoline derivatives have been found to act as suicide inhibitors of SSAO, the semicarbazide group in these molecules may be responsible for the SSAO inhibitory action. It is suggested that these compounds cannot enter the first small active site cavity of SSAO and may interact tightly with another binding site or with some other reactive groups present in the molecule. Compound 3e showed the highest inhibitory activity on rat lung SSAO. The novel pyrazoline derivatives may be used to discriminate between Cu- and FAD-containing amine oxidases and may have promising features as anti-Parkinson agents if the SSAO-inhibitory effects can be supported by in vivo studies.
Yabanoglu
S
S
Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
Ucar
G
G
Gokhan
N
N
Salgin
U
U
Yesilada
A
A
Bilgin
A A
AA
D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008168:Lung / Q000201:enzymology*; D008995:Monoamine Oxidase / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D011720:Pyrazoles / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D012663:Semicarbazides / Q000737:chemistry; D013347:Subcellular Fractions
D004791:Enzyme Inhibitors; D011720:Pyrazoles; D012663:Semicarbazides; D006631:Amine Oxidase (Copper-Containing); D008995:Monoamine Oxidase