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通过分子对接发现一种具有天然产物样结构的诱导型一氧化氮合酶抑制剂，其在体内具有潜在的神经保护作用。

Discovery of a natural product-like iNOS inhibitor by molecular docking with potential neuroprotective effects in vivo.

作者信息

Zhong Hai-Jing, Liu Li-Juan, Chong Cheong-Meng, Lu Lihua, Wang Modi, Chan Daniel Shiu-Hin, Chan Philip Wai Hong, Lee Simon Ming-Yuen, Ma Dik-Lung, Leung Chung-Hang

机构信息

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.

Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.

出版信息

PLoS One. 2014 Apr 1;9(4):e92905. doi: 10.1371/journal.pone.0092905. eCollection 2014.

DOI:10.1371/journal.pone.0092905
PMID:24690920
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3972188/
Abstract

In this study, we applied structure-based virtual screening techniques to identify natural product or natural product-like inhibitors of iNOS. The iNOS inhibitory activity of the hit compounds was characterized using cellular assays and an in vivo zebrafish larvae model. The natural product-like compound 1 inhibited NO production in LPS-stimulated Raw264.7 macrophages, without exerting cytotoxic effects on the cells. Significantly, compound 1 was able to reverse MPTP-induced locomotion deficiency and neurotoxicity in an in vivo zebrafish larval model. Hence, compound 1 could be considered as a scaffold for the further development of iNOS inhibitors for potential anti-inflammatory or anti-neurodegenerative applications.

摘要

在本研究中，我们应用基于结构的虚拟筛选技术来鉴定诱导型一氧化氮合酶（iNOS）的天然产物或类天然产物抑制剂。利用细胞试验和体内斑马鱼幼虫模型对命中化合物的iNOS抑制活性进行了表征。类天然产物化合物1抑制脂多糖刺激的Raw264.7巨噬细胞中一氧化氮的产生，且对细胞无细胞毒性作用。值得注意的是，在体内斑马鱼幼虫模型中，化合物1能够逆转MPTP诱导的运动缺陷和神经毒性。因此，化合物1可被视为进一步开发用于潜在抗炎或抗神经退行性应用的iNOS抑制剂的骨架。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c930/3972188/7b72fea5cb43/pone.0092905.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c930/3972188/8a621c8ac34b/pone.0092905.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c930/3972188/479e5feebf7a/pone.0092905.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c930/3972188/6c1151705fc9/pone.0092905.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c930/3972188/082b7d473869/pone.0092905.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c930/3972188/4d4a89d6780f/pone.0092905.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c930/3972188/feed436a6ef0/pone.0092905.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c930/3972188/4c8676684df8/pone.0092905.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c930/3972188/11e81d75b744/pone.0092905.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c930/3972188/7b72fea5cb43/pone.0092905.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c930/3972188/8a621c8ac34b/pone.0092905.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c930/3972188/479e5feebf7a/pone.0092905.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c930/3972188/6c1151705fc9/pone.0092905.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c930/3972188/082b7d473869/pone.0092905.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c930/3972188/4d4a89d6780f/pone.0092905.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c930/3972188/feed436a6ef0/pone.0092905.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c930/3972188/4c8676684df8/pone.0092905.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c930/3972188/11e81d75b744/pone.0092905.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c930/3972188/7b72fea5cb43/pone.0092905.g009.jpg

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