Nine new limonoids (1-9) were isolated from the stem bark of Guarea guidonia (1-4) and Cedrela odorata (5-9). Their structures were elucidated using 1D and 2D NMR and MS data and chemical methods as three A2,B,D-seco-type limonoids (1-3), a mexicanolide (4), three nomilin-type (5-7) limonoids, and two limonol derivatives (8 and 9). A DFT/NMR procedure was used to define the relative configurations of 1 and 3. A surface plasmon resonance approach was used to screen the Hsp90 binding capability of the limonoids, and the A2,B,D-seco-type limonoid 8-hydro-(8S*,9S*)-dihydroxy-14,15-en-chisomicine A, named chisomicine D (1), demonstrated the highest affinity. By means of mass spectrometry data, biochemical and cellular assays, and molecular docking, 1 was found as a type of client-selective Hsp90 inhibitor binding to the C-terminus domain of the chaperone.
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1021/acs.jnatprod.0c01217|
|Codice identificativo ISI:||MEDLINE:33661631|
|Titolo:||Limonoids from Guarea guidonia and Cedrela odorata: Heat Shock Protein 90 (Hsp90) Modulator Properties of Chisomicine D|
|Appare nelle tipologie:||1.1 Articolo in rivista|