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With bioassay-guided fractionation, five new polyprenylated benzoylphloroglucinol derivatives, garcimultiflorone D (1), 18-hydroxygarcimultiflorone D (2), garcimultiflorone E (3), garcimultiflorone F (4), and isogarcimultiflorone F (5), and five known compounds, guttiferone E (6), guttiferone F (7), aristophenone A (8), isoxanthochymol (9), and morelloflavone (10), were isolated from the acetone extract of the twigs of Garcinia multiflora. The compounds were evaluated for their apoptotic effects against HeLa-C3 cells, which have been genetically engineered to produce a fluorescent biosensor capable of detecting caspase-3 activation. Compounds 1 and 3-9 activate caspase-3 in HeLa-C3 cells within 72 h after treatment at a concentration of 100 microM or lower. In particular, compounds 6, 8, and 9 showed strong apoptosis-inducing effects at a concentration of 25 microM.

Four new compounds, paucinervins A-D (1-4), and 15 known ones were isolated from the leaves of Garcinia paucinervis. The structures of the new compounds were elucidated by spectroscopic evidences. All of the 19 compounds were evaluated for their apoptosis-inducing effects using HeLa-C3 cells which have been genetically engineered to possess a fluorescent biosensor capable of detecting caspase-3 activation. Eight of them were found to activate caspase-3 in HeLa-C3 cells within 72 h at the concentration of 25 microM. Moreover, the values of IC50 were measured for all four new compounds on HeLa cells using the MTT assay. Among them, compound 2 (paucinervin B) had the lowest IC50 value of 9.5 microM, while the other three new compounds had much higher IC50 values of 29.5, 52.5, and 95.6 microM, respectively. This result shows that paucinervin B has the strongest inhibitory effect against HeLa cell growth among these four newly identified paucinervins and it may have the potential to be developed into a new anticancer candidate., (Copyright (c) 2010. Published by Elsevier Ltd.)

A screening system, composed of high-speed counter-current chromatography and high-pressure liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry, was established to find bioactive lead compound. This system succeeded in discovering apoptosis inducers from gamboge, the resin of Garcinia hanburyi. High-speed counter-current chromatography was used to provide well-separated fractions for bioassay and the resulted active fractions were rapidly identified using high-pressure liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry. The solvent system of n-hexane/ethyl acetate/methanol/water was optimized to the ratio of 7:3:7:3 (v/v/v/v) by a K value analysis. As a result, two active fractions were obtained. They showed apoptosis inducing effects as potent as that of taxol (500 nM) at the concentration of 1 microg/ml. Gambogenic acid (72.1%) and epimeric isogambogic acids (25.3%) were identified in one of the fractions. The other active fraction mainly contained two epimeric mixtures, gambogic acids (68.7%) and gambogoic acids (26.9%). Among them, gambogenic acid, without epimerization, has priority to be lead compound.

Bioassay and ultraperformance liquid chromatography/photodiode array/mass spectrometry (UPLC/PDA/MS) guided isolation of the apoptosis-inducing active metabolites on HeLa-C3 cells from the pericarp of Garcinia yunnanensis (Guttiferae) yielded five active compounds, including the new garciyunnanins A (1) and B (2). The structures of the compounds were elucidated by comprehensive nuclear magnetic resonance and mass spectrometry analysis. Garciyunnanin B (2), featured with a natural tetracyclic xanthone skeleton derived from a polyisoprenylated benzophenone, is structurally interesting since it can be seen as an evidence of the previously described cyclization of garcinol by 2,2-diphenyl-1-picrylhydrazyl (DPPH). Garciyunnanin A (1) contains a 3-monohydroxy benzophenone skeleton, which is rarely found in Garcinia species. Both new compounds induce HeLa-C3 cells into apoptosis after 72 h of incubation at 15 microM. It is noteworthy that oblongifolin C (4), the major constituent of this plant, has proved to be the most active one among the isolates for inducing apoptotic cell death in cervical cancer derived HeLa-C3 sensor cells.

Three new prenylated xanthones, 1-3, along with ten known compounds, were isolated from the stem bark of Garcinia lancilimba. Their structures were elucidated by extensive spectroscopic analysis, including 1D- and 2D-NMR spectra, as well as HR-MS experiments. Some of these compounds showed apoptotic effects or growth-inhibition effects against HeLa cells expressing a caspase sensor protein.