Peltodon longipes (Labiatae), also known as „baicuru amarelo“ in south of Brazil, has been used in
folk medicine as an anti-inflammatory and antiseptic remedy (1). The effective compounds
responsible for these effects are still unknown. Here we report the isolation and
structure elucidation of 12 diterpenes from the abietane type. 12,14-dihydroxy-11-methoxyabieta-8,11,13-trien-7-one
was isolated for the first time, whereas the other diterpenes have already been known.
Structure elucidation was based on 1D-(1H and 13C) and 2D NMR experiments (COSY, HMQC, HMBC and NOESY) as well as EIMS. Cytotoxic
activity of these compounds was evaluated against two different cancer cell lines,
MIA PaCa-2 (Human Pancreatic Carcinoma Cell Line) and MV-3 (Human Melanoma Cell Line).
7α acetoxyroyleanone, the major compound, showed the highest cytotoxic activity with
an IC50 value of 4.7 and 7.5µM, respectively. Interestingly, some diterpenes preferentially
inhibited topoisomerase-I in the relaxation assay and gave lower IC50 values (2.8 and 4.7µM) than the known classical topoisomerase-I inhibitor camptothecin
(IC50 28µM). Docking experiments revealed that these diterpenes may target topoisomerase-I
differenzially to camptothecin. While camptothecin stabilizes type I topoisomerase-DNA
complexes, there is evidence that the diterpenes compete with DNA for topoisomerase
binding through direct interaction. A new binding side is suggested which allows correlation
with the experimental data. Additionally studies are in progress to give further insights
in the mechanism of action.
Acknowledgements: Financial support from the government Baden-Württemberg (Zukunftsoffensive IV) is
gratefully acknowledged.
References: 1. Mentz, L.A. et al. (1997) Caderno de Farmácia, 13: 25–48.
