Cabreuvanols A-C, three new cassane-derived diterpenes from Myrocarpus frondosus and their anti-inflammatory effects.

Three previously unreported cassane-type diterpenoids (2-4), were purified from Myrocarpus frondosus roots alongside four known compounds (1, 5-7). Their structures were established based on spectroscopic and spectrometric data as cabreuvanols A-C (2-4) and ayapin (1), afromosin 7-O-β-D-apiofuranosyl-(1 → 2)-glucopyranoside (5), thyrsifloside (6) and afromosin 7-O-β-D-glucopyranoside (7). The absolute configuration of compound 2 was determined by using X-ray crystallography experiments. The crude extract (CE), fractions (MF, EAF, and DCMF) and compounds 1-3 were evaluated for their cytotoxicity against the mouse macrophage J774 and their inhibitory effects against inflammatory biomarkers. Except for MF, others showed high CC10 values against the macrophage. On the other hand, compound 3 was more cytotoxic than others. CE and EAF inhibited NOx production at doses of 10, 3, and 1 μg/mL in a range of 82.2 ± 4.2 and 68.6 ± 4.8 %, whereas DCMF displayed almost a constant activity between 78.9 ± 1.0 and 72.7 ± 1.5 % at three doses. Compounds 1 and 2 moderately reduced NOx in a range of 58.6 ± 4.7 and 23.4 ± 8.8 %. These samples also reduced NOx, myeloperoxidase, exudation, and cell migration from the bronchoalveolar lavage in the in vivo experimental model of acute pulmonary inflammation (ALI).