title: Novel bis-(arylsulfonamide) hydroxamate-based selective MMP inhibitors.
abstract: A series of bis-(arylsulfonamide) hydroxamate inhibitors were synthesized. These compounds exhibit good potency against MMP-7 and MMP-9 depending on the nature, steric bulk, and substitution pattern of the substituents in the benzene ring. In general, the preliminary structure-activity relationships (SAR) suggest that among the DAPA hydroxamates (i) electron-rich benzene rings of the sulfonamides may produce better inhibitors than electron-poor analogs. However, potential H-bond acceptors can reverse the trend depending on the isozyme; (ii) isozyme selectivity between MMP-7 and -9 can be conferred through steric bulk and substitution pattern of the substituents in the benzene ring, and (iii) the MMP-10 inhibition pattern of the compounds paralleled that for MMP-9.
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, 1401 Albrecht Blvd, Fargo, ND 58105, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Subramaniam
authors.forename: Manas K
authors.initials: MK
authors.lastname: Haldar
authors.forename: Shakila
authors.initials: S
authors.lastname: Tobwala
authors.forename: Bratati
authors.initials: B
authors.lastname: Ganguly
authors.forename: D K
authors.initials: DK
authors.lastname: Srivastava
authors.forename: Sanku
authors.initials: S
authors.lastname: Mallik
mesh_terms: D015195:Drug Design; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D061965:Matrix Metalloproteinase Inhibitors; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D013449:Sulfonamides