Psoralen Derivatives as Inhibitors of Mycobacterium tuberculosis Proteasome.

ABSTRACT: Protein degradation is a fundamental process in all living organisms. An important part of this system is a multisubunit, barrel-shaped protease complex called the proteasome. This enzyme is directly responsible for the proteolysis of ubiquitin- or pup-tagged proteins to smaller peptides. In this study, we present a series of 92 psoralen derivatives, of which 15 displayed inhibitory potency against the Mycobacterium tuberculosis proteasome in low micromolar concentrations. The best inhibitors, i.e., 8, 11, 13 and 15, exhibited a mixed type of inhibition and overall good inhibitory potency in biochemical assays. N-(cyanomethyl)acetamide 8 (K_i = 5.6 µM) and carboxaldehyde-based derivative 15 (K_i = 14.

SUBMITTER: Rozman K 

PROVIDER: S-EPMC7144120 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature