Literature

Abstract

A set of bisphosphonate matrix metalloproteinase (MMP) inhibitors was investigated for inhibitory activity against several carbonic anhydrase (CA, EC 4.2.1.1) isozymes, some of which are overexpressed in hypoxic tumors. Some of the bisphosphonate revealed to be very potent inhibitors (in the low nanomolar range) of the cytosolic isoform CA II and the membrane-bound CA IX, XII and XIV isozymes, a feature useful for considering them as interesting compounds for bone resorption inhibition applications. We suggest here that it is possible to develop dual enzyme inhibitors bearing bisphosphonate moieties that may target both MMPs and CAs, two families of enzymes involved in tumor formation, growth, and metastasis.

DOI： 10.1016/j.bmcl.2014.04.077

Dual carbonic anhydrase/matrix metalloproteinase inhibitors incorporating bisphosphonic acid moieties targeting bone tumors

Bioorganic & Medicinal Chemistry Letters 2014.0

Arylamino bisphosphonates: Potent and selective inhibitors of the tumor-associated carbonic anhydrase XII

Bioorganic & Medicinal Chemistry Letters 2014.0

Carbonic anhydrase and matrix metalloproteinase inhibitors. Inhibition of human tumor-associated isozymes IX and cytosolic isozyme I and II with sulfonylated hydroxamates

Bioorganic & Medicinal Chemistry 2007.0

New hydroxypyrimidinone-containing sulfonamides as carbonic anhydrase inhibitors also acting as MMP inhibitors

Bioorganic & Medicinal Chemistry Letters 2010.0

Dual Inhibitors of Matrix Metalloproteinases and Carbonic Anhydrases: Iminodiacetyl-Based Hydroxamate−Benzenesulfonamide Conjugates

Journal of Medicinal Chemistry 2008.0

Carbonic anhydrase inhibitors: Inhibition of cytosolic/tumor-associated isoforms I, II, and IX with iminodiacetic carboxylates/hydroxamates also incorporating benzenesulfonamide moieties