title: Synthesis of substituted DL-3(5-benzazolyl)alanines as dopa and alpha-methyldopa analogs and their effects on dopamine beta-hydroxylase, tyrosinase and diphenoloxidase.
abstract: The influence of bioisosteric replacement of catechol moiety of L-Dopa and alpha-Methyldopa with benzimidazole and benzotriazole ring has been examined on dopamine beta-hydroxylase and tyrosinase, in order to evidentiate an inhibitory activity on the synthesis of catecholamines and a possible antihypertensive action. The preliminary results obtained so far showed that inhibition of dopamine hydroxylase occurs at 5 x 10(-4) M concentration for the most active compounds bearing a trifluoromethyl group in the azole ring (2a,c). An analogous result was observed in the case of tyrosinase inhibition with compound 2c, while other compounds (2a,e) were equiactive (92% inhibition) at higher concentration (1 x 10(-3) M). Compound 2c was also the most active in inhibition of diphenoloxidase (83% at 6 x 10(-5) M concentration).
authors.affiliation: Istituto di Chimica Farmaceutica e Tossicologica, Università di Sassari.
authors.forename: M
authors.initials: M
authors.lastname: Loriga
authors.forename: G
authors.initials: G
authors.lastname: Paglietti
authors.forename: F
authors.initials: F
authors.lastname: Sparatore
authors.forename: G
authors.initials: G
authors.lastname: Pinna
authors.forename: A
authors.initials: A
authors.lastname: Sisini
mesh_terms: D000311:Adrenal Glands / Q000201:enzymology; D000818:Animals; D001487:Basidiomycota / Q000201:enzymology; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D004156:Catechol Oxidase / Q000037:antagonists & inhibitors*; D002417:Cattle; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives*; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors*; D007887:Fabaceae / Q000201:enzymology; D066298:In Vitro Techniques; D008750:Methyldopa / Q000031:analogs & derivatives*; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D010946:Plants, Medicinal
chemical_list: D001562:Benzimidazoles; D010649:Phenylalanine; D008750:Methyldopa; D004295:Dihydroxyphenylalanine; D004156:Catechol Oxidase; D004299:Dopamine beta-Hydroxylase; D014442:Monophenol Monooxygenase