LAUSR

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.