Limonoids from Guarea guidonia and Cedrela odorata: Heat Shock Protein 90 (Hsp90) modulator properties of Chisomicine D

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 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.