title: Design and synthesis of potent hydroxamate inhibitors with increased selectivity within the gelatinase family.
abstract: MMP-2 is a validated target for the development of anticancer agents. Herein we describe the synthesis of a new series of potent phenylalanine derived hydroxamates, with increased MMP-2/MMP-9 selectivity compared to analogous hydroxamates described previously. Docking and molecular dynamics experiments have been used to account for this selectivity, and to clarify the role of the triazole ring in the binding process.
authors.affiliation: Departamento de Química y Bioquímica, Facultad de Farmacia, Universidad CEU San Pablo, Urbanización Monteprincipe, 28668 Madrid, Spain. bpaster@ceu.es aramgon@ceu.es.
authors.forename: José María
authors.initials: JM
authors.lastname: Zapico
authors.forename: Anna
authors.initials: A
authors.lastname: Puckowska
authors.forename: Kamila
authors.initials: K
authors.lastname: Filipiak
authors.forename: Claire
authors.initials: C
authors.lastname: Coderch
authors.forename: Beatriz
authors.initials: B
authors.lastname: de Pascual-Teresa
authors.forename: Ana
authors.initials: A
authors.lastname: Ramos
mesh_terms: D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D018093:Gelatinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D061965:Matrix Metalloproteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D010649:Phenylalanine / Q000737:chemistry; D013379:Substrate Specificity; D014230:Triazoles / Q000737:chemistry
chemical_list: D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D014230:Triazoles; D010649:Phenylalanine; D018093:Gelatinases