Inhibition of amine oxidases activity by 1-acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives.
A novel series of 1-acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives have been synthesised and investigated for the ability to inhibit selectively monoamine oxidases, swine kidney oxidase, and bovine serum amine oxidase. The newly synthesised compounds 1-6 proved to be reversible and non-competitive inhibitors of all types of the assayed amine oxidases. Compounds inhibit monoamine oxidases potently, displaying low I(50) values of particular interest. In particular 1-acetyl-3-(2,4-dihydroxyphenyl)-5-(3-methylphenyl)-4,5-dihydro-(1H)-pyrazole 6 showed to be a potent monoamine oxidase inhibitor with a K(i) of about 10(-8)M. Further insights in the theoretical evaluation of the possible interactions between the compounds and monoamine oxidase B have been developed through a computational approach.
Manna
Fedele
F
Dipartimento di Studi di Chimica e Tecnologia delle Sostanze Biologicamente Attive, Università di Roma La Sapienza, P.le Aldo Moro 5, Italy. fedele.manna@uniroma1.it
Chimenti
Franco
F
Bolasco
Adriana
A
Secci
Daniela
D
Bizzarri
Bruna
B
Befani
Olivia
O
Turini
Paola
P
Mondovi
Bruno
B
Alcaro
Stefano
S
Tafi
Andrea
A
D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors; D000818:Animals; D002417:Cattle; D008958:Models, Molecular; D008995:Monoamine Oxidase / Q000737:chemistry*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013552:Swine
D008996:Monoamine Oxidase Inhibitors; D011720:Pyrazoles; D006631:Amine Oxidase (Copper-Containing); D008995:Monoamine Oxidase