title: Identification of plant-derived natural products as potential inhibitors of the Mycobacterium tuberculosis proteasome.
abstract: BACKGROUND
  The Mycobacterium tuberculosis (Mtb) proteasome has been established as a viable target for the development of anti-tuberculosis agents. In this study, the inhibitory activities of 100 plant-derived natural products on the Mtb proteasome were analyzed to identify novel potential inhibitors.
  
  
  METHODS
  The fluorescent substrate Suc-Leu-Leu-Val-Tyr-AMC can be hydrolyzed by the proteasome to release free AMC, the fluorescence of which is proportional to the proteasome activity. The inhibitory activities of 100 natural products (each at a final concentration of 200 μM) were detected by this method using MG132 as a positive control.
  
  
  RESULTS
  Twelve of these natural products (10 of which were flavonoids) inhibited the activity of the Mtb proteasome by more than 65%. Comparison of the structural differences between the flavonoids with good inhibitory activity and those without inhibitory activity revealed that the hydroxyl at the flavonoid C ring C-3 or the hydroxyl/methoxyl at the flavonoid A ring C-6 were critical for the inhibition of proteasomal activity.
  
  
  CONCLUSIONS
  These data indicate that flavonoids represent a basis for rational structural design in the process of novel anti-tuberculosis drug discovery.
authors.forename: Yuejuan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Microbiology & Immunology, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China. jiangxingao@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Jiang
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Junxiang
authors.initials: J
authors.lastname: Song
authors.forename: Jinxia
authors.initials: J
authors.lastname: Sun
authors.forename: Lixin
authors.initials: L
authors.lastname: Wang
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Sun
authors.forename: Zhenhui
authors.initials: Z
authors.lastname: Lu
authors.forename: Huiyong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003374:Coumarins / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology; D007976:Leupeptins / Q000737:chemistry; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology; D009842:Oligopeptides / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology*; D010944:Plants / Q000737:chemistry*; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects* / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D001426:Bacterial Proteins; D003374:Coumarins; D005419:Flavonoids; D007976:Leupeptins; D009842:Oligopeptides; D010936:Plant Extracts; D061988:Proteasome Inhibitors; C046582:succinyl-leucyl-leucyl-valyl-tyrosyl-methylcoumarinamide; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde