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 (A1-C3) 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 B2, B3, B4 significantly reduced the growth of cancer cells, in particular, the IC₅₀ values of B3 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, B1, B2, B3 and B4 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, B3 may serve as attractive lead compounds for cancer therapy development.