title: Arylsulfonamides and selectivity of matrix metalloproteinase-2: An overview.
abstract: Uncontrolled regulation of specific metalloenzymes plays important roles in several diseases like tumor metastasis and inflammation. Therefore, selective metalloenzyme inhibition may be a potential target for drug design and development. Matrix metalloproteinase inhibitors (MMPIs) opened up a new horizon as the possible treatment of arthritis, cancer, and emphysema. However, due to adverse effects and poor pharmacokinetics, first generation MMPIs failed in clinical trials. Therefore, development of potential and selective MMPIs is still in demand. Moreover, the flexibility of the enzyme S1' pocket is variable in length and shape making the designing approach more challenging. In this article, arylsulfonamides have been highlighted as potential and selective MMP-2 inhibitors through structure-activity relationships study. It may be postulated that sulfonamide moiety may provide better direction to the associated aryl group to accommodate the deep hydrophobic S1' pocket. Tetrahedral geometry of the sulfonyl function may be favorable than planar carboxyl function regarding the interaction between the aryl group and S1' pocket. Hydroxamates may impart higher inhibition than corresponding carboxylates due to additional hydrogen bonding. Moreover, MMP-2 selectivity is not only dependent on zinc binders but also on the aryl functions directed towards S1 and S2' pockets. Therefore, this review may help in designing potential and selective MMP-2 inhibitors.
authors.affiliation: Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India.
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Adhikari
authors.affiliation: Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India.
authors.forename: Avinaba
authors.initials: A
authors.lastname: Mukherjee
authors.affiliation: Department of Chemical Technology, University of Calcutta, 92, APC Ray Road, Kolkata 700009, India.
authors.forename: Achintya
authors.initials: A
authors.lastname: Saha
authors.affiliation: Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India. Electronic address: tjupharm@yahoo.com.
authors.forename: Tarun
authors.initials: T
authors.lastname: Jha
mesh_terms: D015195:Drug Design; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects*; D061965:Matrix Metalloproteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D013449:Sulfonamides; D020778:Matrix Metalloproteinase 2
keywords: Arylsulfonamide; Matrix metalloproteinase-2; Metalloenzyme; Selectivity; Structure-activity relationship (SAR); Zinc binding group