Germacrone derivatives: synthesis, biological activity, molecular docking studies and molecular dynamics simulations.
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.
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Jie
J
Wu
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Yu
Y
Feng
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Chao
C
Han
Inspection and Quarantine Technology Center of Zhanjiang Entry-Exit Inspection and Quarantine Bureau, Zhanjiang 524001, China.
Wu
W
Huang
School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Zhibin
Z
Shen
School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Mengdie
M
Yang
School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Weiqiang
W
Chen
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Lianbao
L
Ye
D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D030024:Curcuma / Q000737:chemistry*; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D045788:Sesquiterpenes, Germacrane / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D010936:Plant Extracts; D045788:Sesquiterpenes, Germacrane; C048393:germacrone; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
biological activity; c-Met kinase; germacrone derivative; molecular docking; molecular dynamics simulations