Discovery of Novel Bioactive Tanshinones and Carnosol Analogues against Breast Cancer

SIMPLE SUMMARY: Abietane diterpenoids are naturally occurring metabolites isolated from a large variety of plants, and many display antitumor properties. Tanshinones are abietane diterpenoids and were first isolated from Salvia miltiorrhiza “tanshen”, a well-known traditional Chinese medicine, which has been used extensively for the treatment of coronary heart diseases as well as inflammatory diseases. Tanshinone IIA has shown the inhibition of tumor invasion and metastasis in vitro and in vivo, while abietane carnosol found in rosemary (Rosmarinus officinalis) has also exhibited in vitro and in vivo anticancer activities. However, there are few reports on the pharmacological properties of the structural analogues of both molecules. The aim of this study is to synthesize and to evaluate the antitumor activities of analogues of tanshinone and carnosol. In this study, we found that the analogues were able to inhibit the proliferation of four breast cancer cell lines. Our findings show that these readily available analogues can potentially serve as the foundation of an anti-breast cancer therapeutic agent development platform. ABSTRACT: The abietane diterpenoids ferruginol (1), tanshinone IIA (3), and carnosol (4) are well-known for their interesting pharmacological properties, including antitumor, similar to other natural and semisynthetic abietanes. In this study, a pair of semisynthetic C18-functionalized analogues of 3 and 4 were prepared from the commercially available (+)-dehydroabietylamine or readily obtained methyl dehydroabietate. Semisynthetic ferruginol (1) and some selected analogues, together with the synthesized analogues, were tested in vitro for the inhibition of proliferation in four breast cancer cell lines, SUM149, MDA-MB231, T47D, and MCF07. As a result, several tested abietane analogues decreased cell proliferation and enhanced cell death, with IC(50) in the range 1.3–18.7 μM. This work demonstrates the antitumor activities of two tested compounds, making these molecules interesting for the development of new anticancer agents.