New ψ -Santonin Derivatives from Crossostephium chinense and Their Anti-Proliferative Activities against Leishmania major and Human Cancer Cells A549.

Previously, we reported two cytotoxic ψ -santonin-amino acid conjugates isolated from the EtOAc layer of Crossostephium chinense . However, a further phytochemical investigation seems to be required because of the few reports of similar derivatives. In this study, we targeted the 1-BuOH layer, which resulted in the isolation of seven new ψ -santonin derivatives ( 1 - 7 ) together with ten known compounds ( 8 - 17 ). The structures of 1 - 7 were elucidated based on spectroscopic methods, including 1D and 2D NMR experiments ( 1 H, 13 C, DEPT, COSY, HSQC, and HMBC), IR spectrum, and high-resolution electrospray ionization-mass spectrometry (HR-ESI-MS). The stereochemistry of new compounds was confirmed by NOESY and ECD calculations. All isolated compounds were evaluated by in vitro experiments for their anti-proliferative activities against Leishmania major , human lung cancer cell line A549, and Vero cells. As a result, most of the ψ -santonin derivatives, especially 1 - 5 , showed significant cytotoxicity against L. major with a lower IC 50 than the positive control we used (miltefosine).