Limonoids from and : Heat Shock Protein 90 (Hsp90) Modulator Properties of Chisomicine D.

Nine new limonoids (-) were isolated from the stem bark of (-) and (-). Their structures were elucidated using 1D and 2D NMR and MS data and chemical methods as three A2,B,D--type limonoids (-), a mexicanolide (), three nomilin-type (-) limonoids, and two limonol derivatives ( and ). A DFT/NMR procedure was used to define the relative configurations of and . A surface plasmon resonance approach was used to screen the Hsp90 binding capability of the limonoids, and the A2,B,D--type limonoid 8-hydro-(8,9*)-dihydroxy-14,15-en-chisomicine A, named chisomicine D (), demonstrated the highest affinity. By means of mass spectrometry data, biochemical and cellular assays, and molecular docking, was found as a type of client-selective Hsp90 inhibitor binding to the C-terminus domain of the chaperone.