Cytotoxic and NF-?B inhibitory constituents of the stems of Cratoxylum cochinchinense and their semisynthetic analogues.

ABSTRACT: A new caged xanthone (1), a new prenylxanthone (2), seven known xanthones, and a known sterol glucoside were isolated from the stems of Cratoxylum cochinchinense, collected in Vietnam. Compounds 1 and 2 were determined structurally by analysis of their spectroscopic data. In addition, five new (10 and 16-19) and eight known prenylated xanthone derivatives were synthesized from the known compounds ?-mangostin (3) and cochinchinone A (6). Several of these substances were found to be cytotoxic toward HT-29 human colon cancer cells, with the most potent being 3,6-di-O-acetyl-?-mangostin (8, ED50, 1.0 ?M), which was tested further in an in vivo hollow fiber assay, but found to be inactive at the highest dose used (20 mg/kg; ip). Of the substances evaluated in a NF-?B p65 inhibition assay, 1,3,7-trihydroxy-2,4-diisoprenylxanthone (5) exhibited the most potent activity (IC50, 2.9 ?M). In a mitochondrial transmembrane potential assay, two new compounds, 1 (IC50, 3.3 ?M) and 10 (IC50, 1.4 ?M), and two known compounds, 3 (?-mangostin, IC50, 0.2 ?M) and 11 (3,6-di-O-methyl-?-mangostin, IC50, 0.9 ?M), were active. A preliminary analogue development study showed that 3,6-diacetylation and 6-benzoylation both slightly increased the cytotoxicity of ?-mangostin (3), whereas methylation reduced such activity. In contrast, neither acetylation, benzoylation, nor methylation enhanced the cytotoxicity of cochinchinone A (6).

SUBMITTER: Ren Y 

PROVIDER: S-EPMC3103643 | biostudies-other | 2011 May

REPOSITORIES: biostudies-other