Protease inhibitors: synthesis of bacterial collagenase and matrix metalloproteinase inhibitors incorporating succinyl hydroxamate and iminodiacetic acid hydroxamate moieties.
A series of succinyl hydroxamates/bishydroxamates as well as a new structural type of matrix metalloproteinase (MMP)/bacterial protease (BP) inhibitors, incorporating iminodiacetic (IDA) hydroxamate/bishydroxamate moieties, has been synthesized and tested for interaction with four vertebrate proteases, MMP-1, MMP-2, MMP-8 and MMP-9, and a BP, the collagenase isolated from Clostridium histolyticum (ChC). The new derivatives generally showed inhibition constants in the range of 8-62 nM against the five proteases mentioned above.
D003013:Clostridium / Q000201:enzymology; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry*; D007098:Imino Acids / Q000737:chemistry*; D007700:Kinetics; D061965:Matrix Metalloproteinase Inhibitors; D008956:Models, Chemical; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D013053:Spectrophotometry
D006877:Hydroxamic Acids; D007098:Imino Acids; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; C008109:iminodiacetic acid