Cytotoxic lanostane-type triterpenoids from the fruiting bodies of Ganoderma lucidum and their structure-activity relationships

Abstract

We conducted a study of Ganoderma lucidum metabolites and isolated 35 lanostane-type triterpenoids, including 5 new ganoderols (1-5). By spectroscopy, we compared the structures of these compounds with known related compounds in this group. All of the isolated compounds were assayed for their effect against the human breast carcinoma cell line MDA-MB-231 and hepatocellular carcinoma cell line HepG2. Corresponding three-dimensional quantitative structure-activity relationship (3D-QSAR) models were built and analyzed using Discovery Studio. These results provide further evidence for anti-cancer constituents within Ganoderma lucidum, and may provide a theoretical foundation for designing novel therapeutic compounds.

Keywords: 3D-QSAR; Ganoderma lucidum; cytotoxicity; lanostane-type triterpenoids.

Figure 1. Purification procedure of compounds 1-35 from the fruit bodies of G. lucidum

The purification procedure was started with the fruit body of Ganoderma lucidum. Each step is indicated by one arrow. Each Fraction (Fr.) was collected separately for further purification. Each compound (Compd.) was obtained in the final step and stored at -20°C for further analysis.

Figure 2. Structures and names of new compounds 1–5

Figure 3. Key HMBC () and ROESY() correlations of compounds 1−5

Figure 4. Experimental versus predicted breast carcinoma inhibitory activities of the training set and the test set

The well agreement between predicted pIC₅₀ value and experimental pIC₅₀ value for both test sets and training sets indicated that this model was reliable in forecasting activity for G. lucidum triterpenoids.

Figure 5. 3D-QSAR model and docking analysis. a. 3D-QSAR model coefficients of triterpenoids from G

lucidum on van der Waals grids. Green represents positive coefficients; yellow represents negative coefficients. b. 3D-QSAR model coefficients on electrostatic potential grids. Blue represents positive coefficients; red represents negative coefficients. c. 2D diagram of the interaction between compound 3 and the binding site of TNF-α. The H-bond (yellow dash) is displayed. d. 3D diagram of the interaction between compound 3 and the binding site of TNF-α. For clarity, only interacting residues are displayed. The H-bond (yellow dash) is displayed. e. The receptor surface model with compound 3.