Inhibitory effect of 1,3,5-triphenyl-4,5-dihydro-(1H)-pyrazole derivatives on activity of amine oxidases.
A new series of 1,3,5-triphenyl-4,5-dihydro-(1H)-pyrazole derivatives was synthesized to ascertain the contribution of substituted phenyl rings present on the 4,5-dihydro-(1H)-pyrazole nucleus to the monoamine oxidases inhibition and bovine serum amine oxidase inhibition. All compounds were tested on bovine brain mitochondria preparation containing flavin-monoamine oxidases and on purified bovine serum amine oxidases, taken as a model of trihydroxyphenylalanine quinone-copper-containing amine oxidases. The 1,3,5-triphenyl-4,5-dihydro-(1H)-pyrazole derivatives showed a good inhibitory activity and belonged to the third generation of monoamine oxidase inhibitors and bovine serum amine oxidase inhibitors which have the advantage of acting through a reversible mode. Furthermore, their activity showed a good degree of selectivity towards the bovine serum amine oxidase inhibition dependent on the substituents present on the phenyl ring at position 5 of the 4,5-dihydro-(1H)-pyrazole.
Manna
F
F
Dipartimento di Studi di Chimica e Technologia delle Sostanze Biologicamente Attive, Università di Roma La Sapienza, Italy.
Chimenti
F
F
Bolasco
A
A
Bizzarri
B
B
Befani
O
O
Pietrangeli
P
P
Mondovi
B
B
Turini
P
P
D000818:Animals; D001921:Brain / Q000201:enzymology; D002417:Cattle; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D008928:Mitochondria / Q000201:enzymology; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000302:isolation & purification / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019906:Nuclear Magnetic Resonance, Biomolecular; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors* / Q000097:blood / Q000302:isolation & purification; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D008996:Monoamine Oxidase Inhibitors; D011720:Pyrazoles; D008995:Monoamine Oxidase; D000587:Oxidoreductases Acting on CH-NH Group Donors