Synthesis and cytotoxicity evaluation of yunnancoronarin A derivatives

Yunnancoronarin A, a prominent natural labdane diterpene, has a range of pharmacological characteristics. In this study, 11 compounds (<b>A1</b>–<b>C3</b>) were synthesised using an acylation procedure and subsequent photooxidation, with yunnancoronarin A serving as the starting material. The structures of the eleven novel compounds were determined using ¹H NMR,¹³C NMR, and HR-ESI-MS. The cytotoxic activities of these compounds were evaluated against five cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW480) and one normal cell line (Beas2B). The findings indicated that derivatives <b>B2</b>, <b>B3</b>, <b>B4</b> significantly reduced the growth of cancer cells, in particular, the IC₅₀ values of <b>B3</b> against SMMC-7721, A-549, MCF-7 and SW480 cell lines with 2.15, 1.72, 3.17 and 3.49 μM, respectively. The values were significantly lower than the positive control (cisplatin). Furthermore, <b>B1</b>, <b>B2</b>, <b>B3</b> and <b>B4</b> revealed weaker cytotoxic activity against human normal lung epithelial cells (Beas2B) than that against A-549 cells, whilst cisplatin showed stronger cytotoxic activity against Beas2B cells than that against A-549 cells. Structure-activity relationship studies showed that the B ring of yunnancoronarin A can affect the cytotoxicity of the compound. Consequently, <b>B3</b> may serve as attractive lead compounds for cancer therapy development.