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.
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.
Saczewski
Franciszek
F
Department of Chemical Technology of Drugs, Medical University of Gdansk, 80-416 Gdansk, Poland.
Sławiński
Jarosław
J
Kornicka
Anita
A
Brzozowski
Zdzisław
Z
Pomarnacka
Elzbieta
E
Innocenti
Alessio
A
Scozzafava
Andrea
A
Supuran
Claudiu T
CT
D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology*; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D015394:Molecular Structure; D009369:Neoplasms / Q000201:enzymology*; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014867:Water
D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D013449:Sulfonamides; D014867:Water