Caged Garcinia Xanthones: Synthetic Studies and Pharmacophore Evaluation

Chantarasriwong, Oraphin; Althufairi, Bashayer D.; Checchia, Nicholas J.; Theodorakis, Emmanuel A.

doi:10.1016/b978-0-444-64056-7.00004-0

Cited by 6 publications

(3 citation statements)

References 153 publications

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“…[ 2‐3 ] Due to the complex chemical structures and remarkable bioactivities, the caged xanthones have attracted increasing attentions in the past decades. [ 7‐10 ]…”

Section: Background and Originality Contentmentioning

confidence: 99%

Cytotoxic 7‐Methoxylated Caged Xanthones from the Twigs of Garcinia oligantha

Yang

Xiang

et al. 2021

Chin. J. Chem.

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Main observation and conclusion Nineteen unprecedented 7‐methoxylated caged xanthones (1—19) were isolated from the twigs of Garcinia oligantha under the guidance of NMR spectroscopy. Their structures and absolute configurations were demonstrated by extensive spectroscopic data, single‐crystal X‐ray diffraction, electronic circular dichroism (ECD) calculations, and the modified Mosher's method. Compound 1 is a rare scalemic 7‐methoxylated neo‐caged xanthone, which was resolved using HPLC with CD detection on a chiral‐phase AD column, and compounds 2—3 are rare 7‐methoxylated caged xanthones with the hydrogenated Δ8(8a) double bond. Fourteen compounds exhibited promising inhibitory activities against four human cancer cell lines with IC50 values ranging from 1.9 to 14.3 μmol/L. A cell apoptosis analysis using flow cytometry showed that compound 11 could induce apoptosis in a dose dependent manner. Moreover, PARP, caspase‐9, and Bcl‐2 western blotting suggested that compound 11‐induced apoptosis may be involved in caspase‐dependent pathway.

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“…[ 2‐3 ] Due to the complex chemical structures and remarkable bioactivities, the caged xanthones have attracted increasing attentions in the past decades. [ 7‐10 ]…”

Section: Background and Originality Contentmentioning

confidence: 99%

Cytotoxic 7‐Methoxylated Caged Xanthones from the Twigs of Garcinia oligantha

Yang

Xiang

et al. 2021

Chin. J. Chem.

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“…Anti-HIV-1 activity of gambogic acid ( 28 ) and morellic acid ( 31 ), by inhibiting the HIV-1 reverse transcriptase enzyme [62] and the antiatherosclerosis activity of gambogic acid ( 28 ) via inhibition of vascular smooth muscle cell proliferation were also significant [75]. The isolation and biological activity evaluation of these compounds have been extensively reviewed by several groups [76,77,78,79,80].…”

Section: Natural Carboxyxanthone Derivativesmentioning

confidence: 99%

Carboxyxanthones: Bioactive Agents and Molecular Scaffold for Synthesis of Analogues and Derivatives

et al. 2019

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Xanthones represent a structurally diverse group of compounds with a broad range of biological and pharmacological activities, depending on the nature and position of various substituents in the dibenzo-γ-pyrone scaffold. Among the large number of natural and synthetic xanthone derivatives, carboxyxanthones are very interesting bioactive compounds as well as important chemical substrates for molecular modifications to obtain new derivatives. A remarkable example is 5,6-dimethylxanthone-4-acetic acid (DMXAA), a simple carboxyxanthone derivative, originally developed as an anti-tumor agent and the first of its class to enter phase III clinical trials. From DMXAA new bioactive analogues and derivatives were also described. In this review, a literature survey covering the report on carboxyxanthone derivatives is presented, emphasizing their biological activities as well as their application as suitable building blocks to obtain new bioactive derivatives. The data assembled in this review intends to highlight the therapeutic potential of carboxyxanthone derivatives and guide the design for new bioactive xanthone derivatives.

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“…Efforts to isolate the bioactive constituents of gamboge led to the identification of gambogic acid (GBA, Figure 1), an unusual polyprenylated metabolite structurally defined by a tricyclic xanthone backbone (ABC ring system) of which the C-ring has been converted into a cage structure (Yates et al, 1963;Ren et al, 2011;Xu et al, 2017). The seemingly inconspicuous xanthone motif is further decorated by peripheral substitutions and oxidations to produce an ever-growing family of natural products collectively referred to as caged Garcinia xanthones (CGXs) (Chantarasriwong et al, 2010;Anantachoke et al, 2012;Jia et al, 2015;Chantarasriwong et al, 2018;Phang et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Gambogic acid: Multi-gram scale isolation, stereochemical erosion toward epi-gambogic acid and biological profile

et al. 2023

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Introduction: Extracted from gamboge resin, gambogic acid (GBA) is a natural product that displays a complex caged xanthone structure and exhibits promising antitumor properties. However, efforts to advance this compound to clinical applications have been thwarted by its limited availability that in turn, restricts its pharmacological optimization.Methods: We report here an efficient method that allows multigram scale isolation of GBA in greater than 97% diastereomeric purity from various sources of commercially available gamboge. The overall process includes: (a) isolation of organic components from the resin; (b) separation of GBA from the organic components via crystallization as its pyridinium salt; and (c) acidification of the salt to isolate the free GBA.Results and Discussion: We found that GBA is susceptible to epimerization at the C2 center that produces epi-gambogic acid (epi-GBA), a common contaminant of all commercial sources of this compound. Mechanistic studies indicate that this epimerization proceeds via an ortho-quinone methide intermediate. Although the observed stereochemical erosion accounts for the chemical fragility of GBA, it does not significantly affect its biological activity especially as it relates to cancer cell cytotoxicity. Specifically, we measured similar levels of cytotoxicity for either pure GBA or an equilibrated mixture of GBA/ epi-GBA in MBA-MB-231 cells with IC50 values at submicromolar concentration and induction of apoptosis after 12 hours of incubation. The results validate the pharmacological promise of gambogic acid and, combined with the multigram-scale isolation, should enable drug design and development studies.

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Caged Garcinia Xanthones: Synthetic Studies and Pharmacophore Evaluation

Cited by 6 publications

References 153 publications

Cytotoxic 7‐Methoxylated Caged Xanthones from the Twigs of Garcinia oligantha

Cytotoxic 7‐Methoxylated Caged Xanthones from the Twigs of Garcinia oligantha

Carboxyxanthones: Bioactive Agents and Molecular Scaffold for Synthesis of Analogues and Derivatives

Gambogic acid: Multi-gram scale isolation, stereochemical erosion toward epi-gambogic acid and biological profile

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