Design, synthesis and an anti-proliferative activity study of C-14 amide substituted derivatives of dehydroabietic acid.

In this study, a series of new C-14 amide substituted derivatives of dehydroabietic acid were designed, synthesized and evaluated for their anti-proliferative activity. Among them, compound 20 showed the best anti-proliferative activity against four tumor cell lines (A549, HepG2, MCF-7 and HCT-116), with half-maximal inhibitory concentration (IC 50) values ranging from 1.83 μM – 4.58 μM, which were approximately 2.72–6.26 times more potent than 5-fluorouracil (5-FU). Preliminary mechanistic studies suggested that 20 causes cell cycle arrest at the G2/M phase and induces apoptosis of HCT-116 tumor cells in a dose-dependent manner. Western blot analysis demonstrated that compound 20 induced this apoptosis through the intrinsic mitochondrial signaling pathway. These results suggested that abietic acid derivative 20 is a promising starting point for further optimization. [Display omitted] • potent in vitro antitumor activities. • Chemical stable and low toxicity. • Induction of apoptosis in cancer cells. [ABSTRACT FROM AUTHOR]