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

Abstract

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 (1H, 13C, 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 IC50 than the positive control we used (miltefosine).

Keywords

• <i>Crossostephium chinense</i>
• sesquiterpene
• <i>ψ</i>-santonin
• <i>Leishmania major</i>
• A549