Design, synthesis and biological activity of novel Xuetongsu derivatives as potential anticancer agents by inducing apoptosis

Xuetongsu (XTS, Schisanlactone E) is one of the main active compounds and considered as the star molecule isolated from <i>Kadsura heteroclita</i> (Roxb.) Craib. In order to improve XTS anti-tumour bioactivities, a series of novel XTS derivatives were designed and synthesised by introducing an amide bond at the parent. Anti-proliferative assays on four different human tumour cell lines (BGC-823, HepG-2, HCT-116, and MCF-7) showed that the anti-tumour activities of most derivatives increased greatly compared to the parent XTS, and especially, compounds <b>A</b>-<b>7</b>, <b>A</b>-<b>14</b>, and <b>A</b>-<b>18</b> exhibited multiple anti-tumour effects. Among them, compound <b>A</b>-<b>7</b> has the best biological activities on the four tumour cell lines with the IC₅₀ values ranging from 13.86 to 20.71 μM, which could significantly increase the fraction of apoptotic cells according to flow cytometry experience. Further study demonstrated that <b>A</b>-<b>7</b> could induce apoptosis on HepG-2 cells through influencing the key apoptotic related proteins, such as Bcl-2, Bax, and cleaved Caspase-3.