New hydroxypyrimidinone-containing sulfonamides as carbonic anhydrase inhibitors also acting as MMP inhibitors.
A set of benzenesulfonamide (BSA) derivatives bearing a hydroxypyrimidinone (HPM) moiety were synthesized and investigated for their inhibitory activity against several carbonic anhydrase (CA, EC 4.2.1.1) isozymes. They all revealed to be very potent inhibitors (nanomolar order) of the cytosolic CA I and II isozymes, but especially of the transmembrane, tumor-associated CA IX isozyme, a beneficial feature for a potential antitumor effect of these compounds. Further structure optimization aimed at improving the specificity of CA inhibition and enhancing their matrix metalloproteinase (MMP) inhibitory activity may also lead to new compounds with an attractive dual mechanism of action as antitumor agents.
Esteves
M Alexandra
MA
LNEG, Unidade de Pilhas de Combustível e Hidrogénio, Estrada do Paço do Lumiar, Lisboa, Portugal.
Ortet
Osvaldo
O
Capelo
Anabela
A
Supuran
Claudiu T
CT
Marques
Sérgio M
SM
Santos
M Amélia
MA
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II; D000071231:Carbonic Anhydrase IX; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D002256:Carbonic Anhydrases; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D007527:Isoenzymes; D061965:Matrix Metalloproteinase Inhibitors; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D002257:Carbonic Anhydrase Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D061965:Matrix Metalloproteinase Inhibitors; D011744:Pyrimidinones; D013449:Sulfonamides; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases