Synthesis and antitumor activity of novel tanshinone derivatives with amino acid esters

The clinical development of natural product tanshinone for cancer therapy is hindered by its weak potency and poor drug-like properties. In this study, a systematic structural modification of tanshinone I and tanshinone IIA was conducted to generate two series of tanshinone-L-amino acid ester derivatives. Among these, derivatives 3d, 3f, 3i and 3l exhibited the most potent antiproliferative activity against cancer cells, with compound 3f being approximately 108- to 233-fold more potent than tanshinoneI. Extensive studies revealed that compounds 3d, 3f, 3i and 3l induced apoptosis in cancer cells and may involve autophagy pathway. Furthermore, an in silico absorption, distribution, metabolism and excretion (ADME) evaluation was conducted to estimate the drug likeness of synthesised compounds. This research provides new insights into the development of tanshinones as potential anticancer agents.