Abstract
A series of sulfonylated hydroxamates were synthesized and evaluated as dual inhibitors of both human carbonic anhydrases (hCAs) and matrix metalloproteinases (MMPs), two metalloenzyme families involved in carcinogenesis and tumor invasion processes. The new derivatives were tested on three CA isozymes, the cytosolic isozymes I and II, and the transmembrane, tumor-associated isozyme IX, and also on human gelatinases (MMP-2 and MMP-9). Some of the new derivatives proved to be potent and selective inhibitors of CA II, but only compounds 3b and 6b, devoid of the arylsulfonyl moiety, proved to have a better inhibitory activity on hCA IX than on hCA I and II, in the micromolar range.
MeSH terms
-
Animals
-
Carbonic Anhydrase I / antagonists & inhibitors*
-
Carbonic Anhydrase II / antagonists & inhibitors*
-
Cytosol / enzymology
-
Enzyme Inhibitors / chemical synthesis
-
Enzyme Inhibitors / chemistry
-
Enzyme Inhibitors / pharmacology*
-
Humans
-
Hydroxamic Acids / chemical synthesis
-
Hydroxamic Acids / chemistry
-
Hydroxamic Acids / pharmacology*
-
Isoenzymes
-
Matrix Metalloproteinase Inhibitors*
-
Mice
-
Molecular Structure
-
Multiple Myeloma / drug therapy
-
Multiple Myeloma / pathology
-
Structure-Activity Relationship
-
Sulfonic Acids / chemistry*
-
Tumor Cells, Cultured
Substances
-
Enzyme Inhibitors
-
Hydroxamic Acids
-
Isoenzymes
-
Matrix Metalloproteinase Inhibitors
-
Sulfonic Acids
-
Carbonic Anhydrase I
-
Carbonic Anhydrase II