Synthesis of the rearranged abietane diterpenes pygmaeocins C and D, viridoquinone,
saprorthoquinone, and 1-deoxyviroxocine has been successfully achieved. The anticancer and
anti-inflammatory activities of selected orthoquinonic compounds 5, 7, 13, and 19, as well as pygmaeocin
C (17), were evaluated for the first time. The antitumor properties were assessed using
three cancer cell lines: HT29 colon cancer cells, Hep G2 hepatocellular carcinoma cells, and B16-
F10 murine melanoma cells. Compounds 5 and 13 showed the highest cytotoxicity in HT29 cells
(IC50 = 6.69 1.2 g/mL and IC50 = 2.7 0.8 g/mL, respectively). Cytometric studies showed
that this growth inhibition involved phase S cell cycle arrest and apoptosis induction, possibly
through the activation of the intrinsic apoptotic pathway. Morphological apoptotic changes, including
nuclear fragmentation and chromatin condensation, were also observed. Furthermore, the
anti-inflammatory activity of these compounds was evaluated on the basis of their ability to inhibit nitric
oxide production on the lipopolysaccharide activated RAW 264.7 macrophage cell line. Although
all compounds showed high anti-inflammatory activity, with percentages between 40 and 100%, the
highest anti-inflammatory potential was obtained by pygmaeocin B (5) (IC50NO = 33.0 0.8 ng/mL).
Our results suggest that due to their dual roles, this type of compound could represent a new strategy,
contributing to the development of novel anticancer agents.
