Environmental factors can influence secondary plant metabolism, inducing seasonal variation in chemical composition. Few works report how the seasons of Brazilian savanna (Cerrado), rainy and dry, impacts plant metabolism. We investigated the seasonal effect on the production of secondary metabolites in Duguetia furfuracea. Leaves of three individuals were collected monthly for one year and analyzed by ultra-fast liquid chromatography coupled to diode array detector and mass spectrometry (UFLC-DAD-MS), partial least squares-discriminant analysis (PLS-DA), hierarchical cluster analysis (HCA), volcano plot, and Pearson correlation. The main chemical classes found were benzyltetrahydroisoquinoline derivatives and flavonoids. Alkaloids are virtually perennial, with qualitative variation during the year, and flavonoids accumulate during the rainy season. Dew point temperature seemed to be the most representative weather indicator in the metabolite change. These results showed for the first time the effect of the Cerrado environment on the levels of flavonoids and alkaloids in Duguetia furfuracea. They could be useful for exploring this species since it is used in popular medicine and accumulates valuable secondary metabolites.

Abstract The extensive marine biodiversity has proved to be a promising source of substances with biomedical potential. In this study, the cytotoxicity of the Brazilian octocoral Phyllogorgia dilatata (Gorgoniidae) was evaluated against two tumor cell lines and three bacterial strains. The methanol/dichloromethane crude extract presented no antibacterial activity up to the highest concentration tested (512 µg/mL), however it revealed a noteworthy antiproliferative effect against HCT-116 (80%) and MCF-7 (54%) cell lines at 50 μg/mL. Therefore, guided by the cytotoxic activity, a multistep chemical fractionation of the extract provided the subfraction 5 (PDPH2-5) with IC50 values of 3.18 and 17.80 μg/mL against HCT-116 and MCF-7, respectively. The LC-HRMS/MS analysis of PDPH2-5 showed ions of m/z 219.1742 and 219.1743, characterized as (E,E) and (Z,E) germacrone, after a LC-DAD-SPE/NMR analysis of the hexanic fraction and comparisons of NMR data with the literature. Previously reported assessments to the cytotoxic activity of the (E,E)-diastereoisomer disclosed higher IC50 values than that obtained for the PDPH2-5 fraction, suggesting, herein, a potentiated effect of the diastereoisomeric mixture. Such remark encourage further bioactivity studies with stereoisomer mixtures and reduce the urge for compound isolation.

This work describes the first determination of the absolute configuration (AC) of (−)-cubebin by means of electronic circular dichroism (ECD), supported by quantum chemical calculations. The comparison of experimental ECD with the corresponding quantum chemical prediction for the proper diastereoisomer resulted in the definitive assignment of the AC of the naturally occurring (−)-cubebin as (8R,8aR,9S). The challenging determination of the relative configuration (RC) of cubebin based only on experimental nuclear magnetic resonance (NMR) methods is stressed. Computation of the 13C and 1H NMR chemical shifts for all the possible diastereoisomers leads to values of mean absolute error and root mean square deviation that do not allow distinguishing among them. Thus, errors in stereochemical determination can easily occur even when using two-dimensional methods, which clearly demonstrate the complexity of this special case. To determine the RC of this bioactive natural compound with high level of confidence, it was necessary to combine the DP4+ method with X-ray crystallography. Therefore, employing the commonly used empirical methods to determine the AC of (−)-cubebin can easily lead to misassignment of its stereochemistry.