Journal
PHYTOCHEMISTRY
Volume 75, Issue -, Pages 78-89Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phytochem.2011.12.002
Keywords
Pseudrocedrela kotschyi; Trichilia emetica; Meliaceae; Hsp90; SPR; Limonoids; Tetranortriterpenes
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Investigation of roots extracts Pseudrocedrela kotschyi and Trichilia emetica led to identification of 5 limonoid derivatives, Kotschyins D-H, and 11 known compounds. Their structures were elucidated by extensive 1D and 2D NMR experiments in conjunction with mass spectrometry. A surface plasmon resonance (SPR) approach was adopted to screen their Hsp90 binding capability and kotschyin D showed a significant affinity for the chaperone. Therefore, the characterization of the biological activity of kotschyin D by means of a panel of chemical and biological approaches, including limited proteolysis, molecular docking and biochemical and cellular assays, was performed. Our result indicated this compound as a type of client selective Hsp90 inhibitor, directly binding to the middle domain of the protein and possibly preventing its interaction with the activator of Hsp90 ATPase 1 (Aha1). (C) 2011 Elsevier Ltd. All rights reserved.
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