Published in:
Open Access
01-12-2014 | Research article
Identification of plant-derived natural products as potential inhibitors of the Mycobacterium tuberculosis proteasome
Authors:
Yuejuan Zheng, Xin Jiang, Feng Gao, Junxiang Song, Jinxia Sun, Lixin Wang, Xiaoxia Sun, Zhenhui Lu, Huiyong Zhang
Published in:
BMC Complementary Medicine and Therapies
|
Issue 1/2014
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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 μ M) 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.