Evaluation of the Inhibition of other Metalloproteinases by Matrix Metalloproteinase Inhibitors

• Published in: Journal of enzyme inhibition 1999, Vol.14 (6), p.425-435
• Main Authors: Marcotte, Patrick A., Elmore, Ildiko N., Guan, Zhiwen, Magoc, Terrance J., Albert, Daniel H., Morgan, Douglas W., Curtin, Michael L., Garland, Robert B., Guo, Yan, Heyman, H. Robin, Holms, James H., Sheppard, George S., Steinman, Douglas H., Wada, Carol K., Davidsen, Steven K.
• Format: Article
• Language: English
• Subjects: Angiotensin-Converting Enzyme Inhibitors; Animals; Bacterial Proteins; Carboxypeptidases - antagonists & inhibitors; Carboxypeptidases A; Cattle; Hydroxamic acid inhibitors; Hydroxamic Acids - chemical synthesis; Hydroxamic Acids - metabolism; Inhibitory Concentration 50; Leucyl Aminopeptidase - antagonists & inhibitors; Matrix Metalloproteinase Inhibitors; Matrix metalloproteinases; Metalloendopeptidases - antagonists & inhibitors; MMPs; Neprilysin - antagonists & inhibitors; Protease Inhibitors - chemical synthesis; Protease Inhibitors - chemistry; Protease Inhibitors - metabolism; Rabbits; Rats; Swine; Thermolysin - antagonists & inhibitors; Zinc - metabolism
• ISSN: 1475-6366; 8755-5093; 1475-6374; 1029-2462
• DOI: 10.3109/14756369909030333

Abstract Two series of compounds synthesized as specific matrix metalloproteinase (MMP) inhibitors have been evaluated for their inhibition of non-MMPs. In a series of substituted succinyl hydrox-amic acids, some were found to be significant (IC50 < 1 μM) inhibitors of leucine (microsomal) aminopeptidase, neprilysin (3.4.24.11), and thermolysin. Macrocyclic compounds in which the alpha carbon of the succinyl hydroxamate is linked to the side chain of the P2′ amino acid were found to be good inhibitors of aminopeptidase, but not of neprilysin or themolysin. Compounds of neither series were found to be significant inhibitors of angiotensin converting enzyme or carboxypeptidase A.