Cytotoxic and Genotoxic Butanolides and Lignans from Aiouea trinervis

Abstract

The ethanolic extracts from the roots, the underground trunk and the leaves of Aiouea trinervis were active in the brine shrimp (Artemia salina) lethality assay (LD₅₀: 1.93, 0.92 and 262.1 μg/mL, respectively). Fractionation of the extracts led to the isolation of four butanolides, namely (-)-epilitsenolides C₂ and C₁ (1 and 2), isoobtusilactone A (3) and obtusilactone A (4), two of which (1 and 2) are reported for the first time as genuine natural products. The lignans (+)-sesamin (5) and (+)-methylpiperitol (6) and polyprenol-12 (7) were isolated as well. Their structures were determined with spectral methods (1D-, 2D-NMR and MS). Compounds 1, 2, 3, 5 and 6 were tested for their cytotoxic activities in Hep₂ human cancer cells. The butanolides 2 and 3 were the most active (IC₅₀: 5.96 μg/mL and 4.95 μg/mL, respectively) whereas the other compounds showed moderate IC₅₀ values ranging from 12.20 μg/mL to 25.64 μg/mL. The genotoxic properties of the crude ethanolic extracts and of compounds 3 and 5 were also evaluated in this study on CHO K1 and HTC mammalian cells with single-cell gel electrophoresis (comet assay). The crude extracts as well as the compounds tested induced DNA migration in this assay, which was indicative of DNA damage (genotoxic effect).

Key words

Aiouea trinervis - Lauraceae - (-)-epilitsenolides C₁ and C₂ - cytotoxic activity - genotoxic activity - comet assay

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