Abstract
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.
Highlights
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)
The Meliaceae, a member of the Sapindales order, is a large family of flowering plants.[1−3] Its main metabolites are the tetranortriterpenoids, known as limonoids, consisting of compounds with variations of the triterpenoid core structure[4,5] and which exhibited a wide range of biological activities,[6] including anticancer and heat-shock protein 90 (Hsp90)
In the past few years, our research group was devoted to the isolation and chemical characterization of limonoids from different Meliaceae species;[7,8] in this context, Guarea guidonia (L.) Sleumer syn
Summary
The stem barks of G. guidonia and C. odorata were extracted with solvents of increasing polarity. Analysis of the 2D NMR spectra, especially the HMBC data, confirmed that 5 was a rearranged nomilin/obacunol-type limonoid with a structure similar to 7-deoxo-7α-acetoxykihadanin A,25 with the only difference being the presence of an additional acetoxy group at C-11. The position of this acetoxy substituent was suggested by the HMBC cross-peak observed between δ 1.32/68.5 (Me-18/C-11) and the COSY correlations between H-9−H-11 and H-11−H2-12, which exhibited proton and carbon resonances for C-11 consistent with the presence of an acetoxy group.
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