title: Synthesis, molecular modeling, and selective inhibitory activity against human monoamine oxidases of 3-carboxamido-7-substituted coumarins.
abstract: A large series of 3-carboxamido-7-substituted coumarins have been synthesized and tested in vitro for their human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitory activity. Taking into account all the relevant structural information on MAOs reported in the literature, we made some changes in the coumarin nucleus and examined with particular attention the effect on activity and selectivity of substituting at position 3 with N-aryl or N-alkyl carboxamide and at position 7 with a benzyloxy or a 4'-F-benzyloxy group. Some of the assayed compounds proved to be potent, selective inhibitors of hMAO-B with IC(50) values in the micromolar range. To better understand the enzyme-inhibitor interaction and to explain the selectivity of the most active compounds toward hMAOs, molecular modeling studies were carried out on new, high resolution, hMAO-A and hMAO-B crystallographic structures.
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Universita degli Studi di Roma La Sapienza, Rome, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Chimenti
authors.forename: Daniela
authors.initials: D
authors.lastname: Secci
authors.forename: Adriana
authors.initials: A
authors.lastname: Bolasco
authors.forename: Paola
authors.initials: P
authors.lastname: Chimenti
authors.forename: Bruna
authors.initials: B
authors.lastname: Bizzarri
authors.forename: Arianna
authors.initials: A
authors.lastname: Granese
authors.forename: Simone
authors.initials: S
authors.lastname: Carradori
authors.forename: Matilde
authors.initials: M
authors.lastname: Yáñez
authors.forename: Francisco
authors.initials: F
authors.lastname: Orallo
authors.forename: Francesco
authors.initials: F
authors.lastname: Ortuso
authors.forename: Stefano
authors.initials: S
authors.lastname: Alcaro
mesh_terms: D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008995:Monoamine Oxidase / Q000737:chemistry*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D003374:Coumarins; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase