Morellic acid

Biomedical Chromatography, 2008, 22(6):637-644.

Improved high-performance liquid chromatographic method for simultaneous determination of 12 cytotoxic caged xanthones in gamboges, a potential anticancer resin fromGarcinia hanburyi.[Reference: WebLink]

The potential anti-tumor activity of gamboges, a herbal medicine derived from Garcinia hanburyi, has increasingly gained the interest of scientist worldwide. The major components of gamboges are cytotoxic caged xanthones.
METHODS AND RESULTS:
In the present study, an improved HPLC method was developed to simultaneously quantify 12 caged xanthones, including three pairs of epimers and four pairs of trans-cis isomers, i.e. forbesione, isoMorellic acid, Morellic acid, R-30-hydroxygambogic acid, S-30-hydroxygambogic acid, isogambogenic acid, gambogenic acid, gambogellic acid, R-isogambogic acid, S-isogambogic acid, R-gambogic acid and S-gambogic acid. This method was validated to be sensitive, precise and accurate with limits of detection of 0.03-0.08 microg/mL, overall intra-day and inter-day variations less than 7.9% and overall recovery over 93.2%. The correlation coefficients (r(2)) of the calibration curves were higher than 0.995 for all analytes. The newly established method was successfully applied to reveal the difference in the chemical profiles and contents of these analytes in gamboges from different origins.
CONCLUSIONS:
It can be concluded that this method was not only an effective quality control method to ensure the safety and efficacy consistency of gamboges, but also a useful tool for screening and determining more potent cytotoxic xanthones with potential anticancer activity.

Molecules, 2013, 18(12):15305-15313.

n Vitro and In Vivo Antiangiogenic Activity of Caged Polyprenylated Xanthones Isolated from Garcinia hanburyi Hook. f.[Reference: WebLink]

Eleven known caged polyprenylated xanthones 1-11 were isolated from the resin of Garcinia hanburyi Hook. f., and their structures were identified by their MS, NMR and UV spectra.
METHODS AND RESULTS:
These xanthones showed significant cytotoxicities against four human cancer cell lines (HeLa, A549, HCT-116, and HepG-2) and strong inhibition against the proliferation of the HUVEC cell line in vitro by the MTT method. Furthermore, in an in vivo zebrafish model, xanthones 3 (Morellic acid), 7 (gambogenin) and 9 (isogambogenic acid) showed comparable antiangiogenic activities with less toxicities than xanthone 1 (gambogic acid), as evaluated by death and heart rates of treated zebrafish. Xanthone 7 exhibited antiangiogenic activity with no toxicity at concentrations ranging from 8 µM to 16 µM. Meanwhile, xanthones 1, 3, 7 and 9 strongly inhibited the migration of HUVEC at a low concentration of 0.5 µM in HUVEC cell migration assay in vitro.
CONCLUSIONS:
Taken together, these findings strongly suggest that xanthone 7 might be a novel angiogenesis inhibitor.

Journal of Chromatographic Science, 2015,53(10) 1695–1700.

Validation of an HPLC-MS-MS Assay for Determination of Morellic Acid in Rat Plasma: Application to Pharmacokinetic Studies.[Reference: WebLink]

A selective and rapid high-performance liquid chromatography-tandem mass spectrometry (HPLC–MS-MS) was developed for the quantification of Morellic acid in rat plasma.
METHODS AND RESULTS:
HPLC was performed using a Capcell MG C18 (50 × 4.6 mm, i.d., 5 µm) column, and isocratic elution with water–acetonitrile (20:80, v/v) at a flow rate of 0.5 mL/min. Sample preparation of analyte and internal standard (gambogic acid) involved liquid–liquid extraction using ethyl acetate–isopropanol (1:1, v/v) from 50 µL plasma. The precursor → production transitions for analyte and IS were m/z 559.4 → 471.3, and m/z 627.3 → 583.3, respectively, and were monitored on a triple-quadrupole mass spectrometer, operating in negative ion scan mode. The method was validated across the dynamic concentration range of 20–7,500 ng/mL for Morellic acid, with a fast run time of 6.0 min. The analytical method measured concentrations of Morellic acid with accuracy (% bias) of ≤6.4% and precision (% RSD) of ≤14.0%. Morellic acid was stable during the battery of stability studies. Finally, the applicability of this assay has been successfully demonstrated in vivo pharmacokinetic studies in Sprague–Dawley rats.
CONCLUSIONS:
This method will therefore be useful for further preclinical and clinical pharmacokinetic studies of Morellic acid.

Journal of Natural Products, 2011, 74(3):460-463.

Absolute configuration of (-)-gambogic acid, an antitumor agent.[Reference: WebLink]

METHODS AND RESULTS:
(-)-Gambogic acid (1), a biologically active "caged xanthone" from gamboge, the dried resin of Garcinia hanburyi, is of interest as a potential anticancer agent. The planar structure of (-)-gambogic acid has been determined previously by analysis of its detailed NMR data and confirmed by single-crystal X-ray diffraction, with the absolute configuration at C-13 deduced as R through a series of chemical degradations.
CONCLUSIONS:
Using (-)-Morellic acid (2), an analogue of (-)-gambogic acid, as a model compound, the 5R, 7S, 10aS, 13R, 27S absolute configuration of (-)-gambogic acid was determined for the first time by comparison of physical and spectroscopic data, especially experimental and calculated electronic circular dichroism.