Discovery of Novel Bioactive Tanshinones and Carnosol Analogues against Breast Cancer.

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 IC50 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.

Triterpenoids as Reactive Oxygen Species Modulators of Cell Fate.

The triterpenoid natural products have played an important role in understanding mechanistic models of human diseases. These natural products are diverse, but many have been characterized as reactive oxygen species (ROS) modulators. ROS can regulate cell survival and function, which ultimately affects biological processes leading to disease. The triterpenoids offer an untapped source of creativity to generate tool compounds with high selectivity to regulate ROS. This brief Review highlights the diverse complexity by which these secondary metabolites induce many cell death modalities (apoptosis, autophagy, ferroptosis, etc.) that can affect various complex cell signaling pathways through ROS and ultimately lead to evading or accelerating cell death.