Identification of plant-derived natural products as potential inhibitors of the Mycobacterium tuberculosis proteasome

BMC Complementary and Alternative Medicine

Research Article

Junxiang Song¹  Lixin Wang¹  Xin Jiang¹  Yuejuan Zheng¹  Xiaoxia Sun¹  Jinxia Sun¹  Zhenhui Lu²  Huiyong Zhang²  Feng Gao³ 

[1] Department of Microbiology & Immunology, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, 201203, Shanghai, China;Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 200032, Shanghai, The People’s Republic of China;Shanghai First People’s Hospital, Shanghai Jiao Tong University, 200080, Shanghai, The People’s Republic of China;

关键词: Mycobacterium tuberculosis;    Proteasome inhibitor;    Plant-derived natural products;    Flavonoids;   

DOI  :  10.1186/1472-6882-14-400

 received in 2014-08-02, accepted in 2014-10-07,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsThe 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.ResultsTwelve 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.ConclusionsThese data indicate that flavonoids represent a basis for rational structural design in the process of novel anti-tuberculosis drug discovery.

【 授权许可】

Unknown   
© Zheng et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.