title: Synthesis and biological evaluation in U87MG glioma cells of (ethynylthiophene)sulfonamido-based hydroxamates as matrix metalloproteinase inhibitors.
abstract: Matrix metalloproteinases (MMPs) are important factors in gliomas since these enzymes facilitate invasion into the surrounding brain and participate in neovascularization. In particular, the gelatinases (MMP-2 and MMP-9), and more recently MMP-25, have been shown to be highly expressed in gliomas and have been associated with disease progression. Thus, inhibition of these MMPs may represent a promising non-cytotoxic approach to glioma treatment. We report herein the synthesis and biological evaluation of a series of 4-butylphenyl(ethynylthiophene)sulfonamido-based hydroxamates. Among the new compounds tested, a promising derivative, 5a, was identified, which exhibits nanomolar inhibition of MMP-2, MMP-9, and MMP-25, but weak inhibitory activity toward other members of the MMP family. This compound also exhibited anti-invasive activity of U87MG glioblastoma cells at nanomolar concentrations, without affecting cell viability.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Pisa, via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Nuti
authors.forename: Francesca
authors.initials: F
authors.lastname: Casalini
authors.forename: Salvatore
authors.initials: S
authors.lastname: Santamaria
authors.forename: Pamela
authors.initials: P
authors.lastname: Gabelloni
authors.forename: Sara
authors.initials: S
authors.lastname: Bendinelli
authors.forename: Eleonora
authors.initials: E
authors.lastname: Da Pozzo
authors.forename: Barbara
authors.initials: B
authors.lastname: Costa
authors.forename: Luciana
authors.initials: L
authors.lastname: Marinelli
authors.forename: Valeria
authors.initials: V
authors.lastname: La Pietra
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: M
authors.initials: M
authors.lastname: Margarida Bernardo
authors.forename: Rafael
authors.initials: R
authors.lastname: Fridman
authors.forename: Federico
authors.initials: F
authors.lastname: Da Settimo
authors.forename: Claudia
authors.initials: C
authors.lastname: Martini
authors.forename: Armando
authors.initials: A
authors.lastname: Rossello
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000737:chemistry; D015194:Diffusion Chambers, Culture; D004338:Drug Combinations; D058851:GPI-Linked Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D007797:Laminin / Q000737:chemistry; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D053504:Matrix Metalloproteinases, Membrane-Associated / Q000737:chemistry / Q000378:metabolism; D062105:Molecular Docking Simulation; D009457:Neuroglia / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D011509:Proteoglycans / Q000737:chemistry; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; D058851:GPI-Linked Proteins; D006877:Hydroxamic Acids; D007797:Laminin; D061965:Matrix Metalloproteinase Inhibitors; D011509:Proteoglycans; D013449:Sulfonamides; D013876:Thiophenes; C059485:matrigel; D003094:Collagen; D053504:Matrix Metalloproteinases, Membrane-Associated; C403928:matrix metalloproteinase 25; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9