海绵中提取的异臭椿萜类化合物作用靶标的识别

引用本文: 田然, 刘振明, 张亮仁, 林文翰, 海绵中提取的异臭椿萜类化合物作用靶标的识别[J]. 物理化学学报, 2011, 27(05): 1214-1222. doi: 10.3866/PKU.WHXB20110525 shu

Citation: TIAN Ran, LIU Zhen-Ming, JIN Hong-Wei, ZHANG Liang-Ren, LIN Wen-Han. Target Identification of Isomalabaricane Terpenes Extracted from Sponges[J]. Acta Physico-Chimica Sinica, 2011, 27(05): 1214-1222. doi: 10.3866/PKU.WHXB20110525 shu

海绵中提取的异臭椿萜类化合物作用靶标的识别

通讯作者: , whlin@bjmu.edu.cn

基金项目:
重大新药创制国家科技重大专项(2009ZX09501-002) (2009ZX09501-002)

国家自然科学基金 (20802006)资助项目 (20802006)

摘要:

采取了包括化学结构相似性学习、靶标聚类分析以及反向对接筛选等多种方法在内的综合性策略, 尝试对中国南海海绵中提取得到的异臭椿萜类化合物进行生物学活性和作用靶标的预测. 结果表明: 这类化合物具有治疗心肌缺血和抗肿瘤的潜在生物学活性; 表皮细胞生长因子受体(EGFR), 焦点(局部)粘着斑激酶(FAK), 胰岛素样生长因子1受体 (IGF1-R), c-Src激酶以及血管表皮生长因子受体2 (VEGF-R2)是这类化合物可能的作用靶标. IC₅₀值从0.41 g·m^-3 (0.41 μg·mL^-1)到9.8 g·m^-3 (9.8 μg·mL^-1)不等. 活性数据显示这些海绵提取的海洋天然产物可作为先导化合物, 通过进一步的优化获得新的药物. 同时还讨论了化合物与预测靶标的结合模式, 结果显示四个化合物都与相应的受体有较好的结合.

关键词:

English

Target Identification of Isomalabaricane Terpenes Extracted from Sponges

1.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, P. R. China

Corresponding author: LIN Wen-Han, whlin@bjmu.edu.cn

Received Date: 22 November 2010
Available Online: 28 April 2011
Fund Project:
重大新药创制国家科技重大专项(2009ZX09501-002)

国家自然科学基金 (20802006)资助项目

Abstract:

A strategy combining structure alignment and comparation, target cluster, and invert-docking screening were undertaken to detect the potential bioactivities of several isomalabaricane triterpenoids that were extracted from sponge. The prediction results revealed that the chemicals underwent myocardial ischemia treatment and had antineoplastic bioactivities. Enzymatic bioassays showed that epidermal growth factor receptor (EGFR), focal adhesion kinase (FAK), insulin-like growth factor 1 receptor (IGF1-R), c-Src kinase, and vascular endothelial growth factor receptor 2 (VEGF-R2) were potential targets for these compounds. They had IC₅₀ values ranging from 0.41 g·m^-3 (0.41 μg·mL^-1) to 9.8 g·m^-3 (9.8 μg·mL^-1), which is meaningful for the use of these marine natural products as leads for further modifications to new agents. Ligand-target binding mode with these compounds were undertaken and indicated that the four studied chemicals bound well with the targets.

Key words:

Marine natural product
/ Isomalabaricane triterpenoid
/ Program of Prediction of Activity Spectra for Substances
/ Reverse virtual screening
/ Target identification
/ Antineoplastic bioactivity

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1.
沈阳化工大学材料科学与工程学院沈阳 110142

海绵中提取的异臭椿萜类化合物作用靶标的识别

通讯作者: , whlin@bjmu.edu.cn

English

Target Identification of Isomalabaricane Terpenes Extracted from Sponges

Corresponding author: LIN Wen-Han, whlin@bjmu.edu.cn

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

海绵中提取的异臭椿萜类化合物作用靶标的识别

通讯作者: , whlin@bjmu.edu.cn

English

Target Identification of Isomalabaricane Terpenes Extracted from Sponges

Corresponding author: LIN Wen-Han, whlin@bjmu.edu.cn

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

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通讯作者: 陈斌, bchen63@163.com

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