Carbonic anhydrase inhibitors. Inhibition of the cytosolic human isozymes I and II, and the transmembrane, tumor-associated isozymes IX and XII with substituted aromatic sulfonamides activatable in hypoxic tumors

Franciszek Saczewski; Jarosław Sławiński; Anita Kornicka; Zdzisław Brzozowski; Elzbieta Pomarnacka; Alessio Innocenti; Andrea Scozzafava; Claudiu T Supuran

doi:10.1016/j.bmcl.2006.06.064

Carbonic anhydrase inhibitors. Inhibition of the cytosolic human isozymes I and II, and the transmembrane, tumor-associated isozymes IX and XII with substituted aromatic sulfonamides activatable in hypoxic tumors

Bioorg Med Chem Lett. 2006 Sep 15;16(18):4846-51. doi: 10.1016/j.bmcl.2006.06.064. Epub 2006 Jun 30.

Authors

Franciszek Saczewski¹, Jarosław Sławiński, Anita Kornicka, Zdzisław Brzozowski, Elzbieta Pomarnacka, Alessio Innocenti, Andrea Scozzafava, Claudiu T Supuran

Affiliation

¹ Department of Chemical Technology of Drugs, Medical University of Gdansk, 80-416 Gdansk, Poland.

PMID: 16809036
DOI: 10.1016/j.bmcl.2006.06.064

Abstract

Some 2-mercapto-substituted-benzenesulfonamides and their disulfides/sulfones were prepared and investigated as inhibitors of four isoforms of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), that is, CA I and II (cytosolic enzymes), and the tumor-associated CA IX and XII. Some mercaptans led to a consistent increase of inhibitory power (52.8- to 243-fold) over the corresponding oxidized (S-S type) derivatives, acting as potential hypoxia-activatable drugs.

MeSH terms

Carbonic Anhydrase Inhibitors / chemical synthesis*
Carbonic Anhydrase Inhibitors / chemistry
Carbonic Anhydrase Inhibitors / pharmacology*
Cell Hypoxia / drug effects
Cell Membrane / drug effects
Cell Membrane / enzymology*
Cytosol / drug effects
Cytosol / enzymology*
Humans
Isoenzymes / antagonists & inhibitors
Isoenzymes / metabolism
Molecular Structure
Neoplasms / enzymology*
Sulfonamides / chemical synthesis
Sulfonamides / chemistry*
Sulfonamides / pharmacology*
Water

Substances

Carbonic Anhydrase Inhibitors
Isoenzymes
Sulfonamides
Water