Dual targeting of cancer-related human matrix metalloproteinases and carbonic anhydrases by chiral N-(biarylsulfonyl)-phosphonic acids. (1st January 2017)

• Record Type: Journal Article
• Authors: Luisi, Grazia; Angelini, Guido; Gasbarri, Carla; Laghezza, Antonio; Agamennone, Mariangela; Loiodice, Fulvio; Supuran, Claudiu T.; Campestre, Cristina; Tortorella, Paolo
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 32:Number 1(2017)
• Page Start: 1260
• Page End: 1264
• Publication Date: 2017-01-01
• Subjects: Carbonic anhydrases -- matrix metalloproteinases -- phosphonic acids -- sulfonamides -- zinc-binding group; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2017.1378192
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: A series of nanomolar phosphonate matrix metalloproteinase (MPP) inhibitors was tested for inhibitory activity against a panel of selected human carbonic anhydrase (CA, EC 4.2.1.1) isozymes, covering the cancer-associated CA IX and XII. None of the reported sulfonyl and sulfonylamino-derivatives sensitively affected the catalytic activity of the cytosolic isoforms CA I and II, which are considered off-target isoforms in view of their physiological role. The most active inhibitors were in the series of chiral N -(sulfonyl)phosphovaline derivatives, which showed good to excellent inhibitory activity over target CAs, with compound15 presenting the best isoform-selectivity toward CA IX. We suggest here that the phosphonates have the potential as dual inhibitors of MMPs and CAs, both involved in tumor formation, invasion and metastasis.