Oncotarget

Research Papers:

Germacrone derivatives: synthesis, biological activity, molecular docking studies and molecular dynamics simulations

Jie Wu, Yu Feng, Chao Han, Wu Huang, Zhibin Shen, Mengdie Yang, Weiqiang Chen and Lianbao Ye _

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Oncotarget. 2017; 8:15149-15158. https://doi.org/10.18632/oncotarget.14832

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Abstract

Jie Wu1, Yu Feng1, Chao Han1, Wu Huang3 , Zhibin Shen4, Mengdie Yang2, Weiqiang Chen2, Lianbao Ye1

1School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China

2School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou 510006, China

3Inspection and Quarantine Technology Center of Zhanjiang Entry-Exit Inspection and Quarantine Bureau, Zhanjiang 524001, China

4School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China

Correspondence to:

Lianbao Ye, email: [email protected]

Keywords: germacrone derivative, biological activity, c-Met kinase, molecular docking, molecular dynamics simulations

Received: September 30, 2016     Accepted: January 13, 2017     Published: January 27, 2017

ABSTRACT

Germacrone is one of the major bioactive components in the Curcuma zedoaria oil product, which is extracted from Curcuma zedoaria Roscoe, known as zedoary. The present study designed some novel germacrone derivatives based on combination principles, synthesized these compounds, and investigated their inhibitions on Bel-7402, HepG2, A549 and HeLa cells. Meanwhile, the study evaluated inhibitions of these derivatives on c-Met kinase, which has been detected in a number of cancers. The results suggested that the majority of the compounds showed stronger inhibitory effect on cancers and c-Met kinase than germacrone. Furthermore, our docking experiments analyzed the results and explained the molecular mechanism. Molecular dynamics simulations were then applied to perform further evaluation of the binding stabilities between compounds and their receptors.


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