title: Synthesis, SAR, and biological evaluation of alpha-sulfonylphosphonic acids as selective matrix metalloproteinase inhibitors.
abstract: Eleven simple alpha-sulfonylphosphonates, new analogues of previously reported alpha-sulfonylaminophosphonates, were prepared and tested as MMP inhibitors. The IC(50) values of most of these compounds are in the nanomolar range against MMP-2, -8, -13, and -14. Compound 11 proved to be the most effective inhibitor of MMP-2 (IC(50) = 60 nM), with interesting selectivity versus the antitarget enzymes MMP-3 and MMP-9. The mode of binding of the new phosphonates in the active site of MMP-2 was studied, and variations in inhibition was explained by means of molecular modeling.
authors.affiliation: Dipartimento Farmaco-Chimico, Università degli Studi di Bari, Via Orabona 4, 70126 Bari, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Rubino
authors.forename: Mariangela
authors.initials: M
authors.lastname: Agamennone
authors.forename: Cristina
authors.initials: C
authors.lastname: Campestre
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fracchiolla
authors.forename: Antonio
authors.initials: A
authors.lastname: Laghezza
authors.forename: Fulvio
authors.initials: F
authors.lastname: Loiodice
authors.forename: Elisa
authors.initials: E
authors.lastname: Nuti
authors.forename: Armando
authors.initials: A
authors.lastname: Rossello
authors.forename: Paolo
authors.initials: P
authors.lastname: Tortorella
mesh_terms: D003198:Computer Simulation; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013451:Sulfonic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D063065:Organophosphonates; D013451:Sulfonic Acids; D020782:Matrix Metalloproteinases