Cytotoxic Lignan Esters From The Bark And Roots Of Syzygium Cf. Lineatum

Abstract

In a search for anticancer agents from higher plants, a sample of the dried bark and roots of Syzygium cf. lineatum (Bl.) Merr. & Perry (Myrtaceae) collected in Vietnam showed cytotoxic activity and was selected as a lead. Separation of the methanol extract of this plant sample, using column chromatography guided by the HT-29 human colon cancer cell line, resulted in the isolation and characterization of three new and several known lignan esters and a new triterpene acetate. The structures of the new compounds were elucidated by interpretation of their ECD, IR, UV, NMR, and mass spectra, with those of the known compounds being characterized by comparison of their spectroscopic data with literature values. The conformation and relative configuration of a known lignan, (2S,3S)-2,3-bis[(4-hydroxy-3-methoxyphenyl)methyl]-1,4-butanediol 1,4-diferulate, were confirmed or revised by analysis of the single-crystal X-ray diffraction, with the absolute configuration of all analogues isolated being established by investigation of their specific rotation values and ECD spectra. All compounds isolated in the present study were evaluated for their cytotoxicity against the HT-29 cell line, and several lignan esters were found to be active. A preliminary structure-activity relationship study showed that both the ester groups and the dimeric units are required for these compounds to mediate cytotoxicity against HT-29 cells.