2752-65-0

Basic information

• Product Name: GAMBOGIC ACID
• Synonyms: BETA-GUTTIFERIN;BETA-GUTTILACTONE;GAMBOGIC ACID;GUTTATIC ACID;GUTTIC ACID;(z)-methyl-3-pentenyl)-;1,5-methano-1h,3h,11h-furo(3,4-g)pyrano(3,2-b)xanthene-1-crotonicacid,3a,4,5,;3,3,11-tetramethyl-13-(3-methyl-2-butenyl)-11-(4-7-tetrahydro-8-hydroxy-alph
• CAS NO: 2752-65-0
• Molecular Formula: C₃₈H₄₄O₈
• Molecular Weight: 628.75
• Product Categories: chemical reagent;pharmaceutical intermediate;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract;Inhibitors
• Mol File: 2752-65-0.mol
• Article Data: 1

Chemical Properties

• Melting Point: 88.5°C
• Boiling Point: 586.06°C (rough estimate)
• Flash Point: 251.446 °C
• Appearance: yellow to orange/
• Density: 1.1057 (rough estimate)
• Vapor Pressure: 1.21E-27mmHg at 25°C
• Refractive Index: 1.5290 (estimate)
• Storage Temp.: Store at -20°C
• Solubility: DMSO: ≥10mg/mL
• PKA: 4.58±0.36(Predicted)
• Stability: Stable for 1 year as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 1 month.
• CAS DataBase Reference: GAMBOGIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: GAMBOGIC ACID(2752-65-0)
• EPA Substance Registry System: GAMBOGIC ACID(2752-65-0)

Safety Data

• Hazard Codes: T
• Statements: 25-36/37/38
• Safety Statements: 26-45
• RIDADR: UN 2811 6.1 / PGIII
• WGK Germany: 1
• RTECS: PB9268200
• Hazardous Substances Data: 2752-65-0(Hazardous Substances Data)

Usage

Description

Gambogic acid, with the chemical formula (2752-65-0), is a natural product derived from Garcinia hanburyi. It is a primary reference substance with assigned absolute purity, taking into account chromatographic purity, water, residual solvents, and inorganic impurities. The exact purity value can be found on the certificate provided by PhytoLab GmbH & Co. KG. Gambogic acid is known for its potent anti-cancer, anti-inflammatory, and cytotoxic properties, making it a promising candidate for various pharmaceutical applications.

Uses

Used in Pharmaceutical Industry:
Gambogic acid is used as an anti-cancer agent for its ability to induce apoptosis in a variety of cell lines, acting as an antagonist of Bcl-2 family proteins with an IC50 of less than 1 mM. It suppresses cancer invasion and migration by inhibiting TGFb1-induced epithelial-to-mesenchymal transition. Additionally, it potentiates the chemosensitivity of cancer cells to other agents and down-regulates the expression of the Survivin protein, reversing docetaxel resistance in cancer cells.
Used in Anti-inflammatory Applications:
Gambogic acid is used as an anti-inflammatory agent due to its ability to reduce inflammation and alleviate pain associated with various conditions.
Used in Cytotoxic Applications:
Gambogic acid is used as a cytotoxic agent for its ability to inhibit the growth and proliferation of cancer cells, particularly HeLa cells in vitro.
Used in Drug Delivery Systems:
Similar to gallotannin, Gambogic acid can also be incorporated into novel drug delivery systems to enhance its applications and efficacy against cancer cells. Various organic and metallic nanoparticles can be employed as carriers for Gambogic acid delivery, aiming to improve its delivery, bioavailability, and therapeutic outcomes.

Biological Activity

Natural product isolated from the Garcinia hanburyi tree. Induces apoptosis in several tumor cell lines including T47D cells. Activates caspases with an EC 50 value of 0.78-1.64 μ M and competitively inhibits antiapoptotic Bcl-2 family proteins (IC 50 values are 1.47, 1.21, 2.02, 0.66, 1.06 and 0.79 μ M for Bcl-XL, Bcl-2, Bcl-W, Bcl-B, Bfl-1 and Mcl-1 respectively). Also blocks K IR 2.1 channels (EC 50 ≤ 100 nM).

Biochem/physiol Actions

Gambogic acid acts as a caspase activator and apoptosis inducer, which causes an irreversible arrest in the G2/M phase of the cell cycle.

Anticancer Research

Gambogic acid is a xanthonoid, also known as kokum that is a resin from Garciniaindica, that can inhibit the proliferation of human breast, hepatoma, lung, and gastriccarcinoma cells. It is also an apoptotic inducer and inhibits telomerase and theexpression of telomerase reverse transcriptase mRNA and its promoter. It also suppressesCDK7-mediated CDC2/p34 phosphorylation, downregulates Bcl-2, andinteracts with c-myc. By interacting with transferrin receptors, it mediates apoptosisof cancer cells. It inhibits NF-κB pathway. In vivo and in vitro experiments determinedits potential to inhibit angiogenesis and VGEF-2 receptor, and thus it inhibitshuman endothelial cell growth, invasion, and migration, microvessel growth, andtube formation (Zhang et al. 2004; Pandey et al. 2007; Aggarwal et al. 2008).GA, extract from Garcinia hanburyi, the most important active constituent of gamboge,inhibits the heat shock protein (Hsp90) (Zhang 2010). Hsp90 is the majorprotein in tumour regeneration as well as cell signalling, and its inhibition results ininduction of ER stress, thereby activating UPR target genes and ER stress sensorswhich further cause cell death (Lamoureux et al. 2014). Severe or sustained ERstress increases CHOP expression and stimulates IRE1α apoptotic signalling, ATF6and PERK. CHOP being the major regulator of Bcl2, Bim and DR5 leads to cellularapoptosis preventing tumour progression (Krajarng et al. 2015).

References

1) Zhai et al. (2008), Gambogic acid is an antagonist of antiapoptotic Bcl-2 family proteins; Mol. Cancer Ther. 7 1639 2) Zhao et al. (2017), Gambogic acid suppresses cancer invasion and migration by inhibiting TGFβ1-induced epithelial-to-mesenchymal transition; Oncotarget 8 27120 3) Wei et al. (2017), Gambogic acid potentiates the chemosensitivity of colorectal cancer cells to 5-fluorouracil by inhibiting proliferation and inducing apoptosis; Exp. Ther. Med. 13 662 4) Wang et al. (2008), Gambogic acid, a potent inhibitor of surviving, reverses docetaxel resistance in gastric cancer cells; Cancer Lett. 262 214

InChI:InChI=1/C38H44O8/c1-20(2)10-9-15-36(8)16-14-24-29(39)28-30(40)26-18-23-19-27-35(6,7)46-37(33(23)41,17-13-22(5)34(42)43)38(26,27)45-32(28)25(31(24)44-36)12-11-21(3)4/h10-11,13-14,16,18,23,27,39H,9,12,15,17,19H2,1-8H3,(H,42,43)/b22-13-/t23?,27?,36-,37?,38-/m1/s1

Downstream Products

• 1398663-14-3 methyl (2Z)-4-[(1R,3aS,5S,11R,14aS)-3a,4,5,7-tetrahydro-8-methoxy-3,3,11-trimethyl-13-(3-methylbut-2-en-1-yl)-11-{(3E)-4-methyl-5-[(4-methylphenyl)amino]pent-3-en-1-yl}-7,15-dioxo-3H,11H-1,5-methanofuro[3,4-g]pyrano[3,2-b]xanthen-1-yl]-2-methylbut-2-enoate 
• 1398663-17-6 methyl (2Z)-4-[(1R,3aS,5S,11R,14aS)-3a,4,5,7-tetrahydro-8-methoxy-11-{(3E)-5-[(4-methoxyphenyl)amino]-4-methylpent-3-en-1-yl}-3,3,11-trimethyl-13-(3-methylbut-2-en-1-yl)-7,15-dioxo-3H,11H-1,5-methanofuro[3,4-g]pyrano[3,2-b]xanthen-1-yl]-2-methylbut-2-enoate 
• 1398663-20-1 methyl (2Z)-4-[(1R,3aS,5S,11R,14aS)-11-{(3E)-5-[(4-chlorophenyl)amino]-4-methylpent-3-en-1-yl}-3a,4,5,7-tetrahydro-8-methoxy-3,3,11-trimethyl-13-(3-methylbut-2-en-1-yl)-7,15-dioxo-3H,11H-1,5-methanofuro[3,4-g]pyrano[3,2-b]xanthen-1-yl]-2-methylbut-2-enoate 
• 1398663-23-4 methyl (2Z)-4-[(1R,3aS,5S,11R,14aS)-3a,4,5,7-tetrahydro-8-methoxy-3,3,11-trimethyl-13-(3-methylbut-2-en-1-yl)-11-{(3E)-4-methyl-5-[(3-nitrophenyl)amino]pent-3-en-1-yl}-7,15-dioxo-3H,11H-1,5-methanofuro[3,4-g]pyrano[3,2-b]xanthen-1-yl]-2-methylbut-2-enoate 
• 1415677-83-6 methyl (2Z)-4-[(1R,3aS,5S,11R,14aS)-3a,4,5,7-tetrahydro-8-methoxy-3,3,11-trimethyl-13-{(2E)-3-methyl-4-[(3-nitrophenyl)amino]but-2-en-1-yl}-11-(4-methylpent-3-en-1-yl)-7,15-dioxo-3H,11H-1,5-methanofuro[3,4-g]pyrano[3,2-b]xanthen-1-yl]-2-methylbut-2-enoate 
• 1415677-84-7 methyl (2Z)-4-{(1R,3aS,5S,11R,14aS)-3a,4,5,7-tetrahydro-8-methoxy-3,3,11-trimethyl-11-(4-methylpent-3-en-1-yl)-13-[(2E)-3-methyl-4-(thiazol-5-ylamino)but-2-en-1-yl]-7,15-dioxo-3H,11H-1,5-methanofuro[3,4-g]pyrano[3,2-b]xanthen-1-yl}-2-methylbut-2-enoate 
• 1415677-85-8 methyl (2Z)-4-[(1R,3aS,5S,11R,14aS)-3a,4,5,7-tetrahydro-8-methoxy-3,3,11-trimethyl-13-{(2E)-3-methyl-4-[(4-methylphenyl)amino]but-2-en-1-yl}-11-(4-methylpent-3-en-1-yl)-7,15-dioxo-3H,11H-1,5-methanofuro[3,4-g]pyrano[3,2-b]xanthen-1-yl]-2-methylbut-2-enoate 
• 1415677-86-9 methyl (2Z)-4-[(1R,3aS,5S,11R,14aS)-3a,4,5,7-tetrahydro-8-methoxy-13-{(2E)-4-[(4-methoxyphenyl)amino]-3-methylbut-2-en-1-yl}-3,3,11-trimethyl-11-(4-methylpent-3-en-1-yl)-7,15-dioxo-3H,11H-1,5-methanofuro[3,4-g]pyrano[3,2-b]xanthen-1-yl]-2-methylbut-2-enoate 
• 1415677-87-0 methyl (2Z)-4-[(1R,3aS,5S,11R,14aS)-13-{(2E)-4-[(4-chlorophenyl)amino]-3-methylbut-2-en-1-yl}-3a,4,5,7-tetrahydro-8-methoxy-3,3,11-trimethyl-11-(4-methylpent-3-en-1-yl)-7,15-dioxo-3H,11H-1,5-methanofuro[3,4-g]pyrano[3,2-b]xanthen-1-yl]-2-methylbut-2-enoate 
• 1393103-22-4 2-deisohexyl-2-(3-(3-nitrophenylamino)-3-oxopropyl)-6-methoxygambogic acid methyl ester 
• 1393103-21-3 2-deisohexyl-2-(3-(4-chlorophenylamino)-3-oxopropyl)-6-methoxygambogic acid methyl ester 
• 1393103-20-2 2-deisohexyl-2-(3-(4-methoxyphenylamino)-3-oxopropyl)-6-methoxygambogic acid methyl ester 
• 1393103-19-9 2-deisohexyl-2-(3-(4-methylphenylamino)-3-oxopropyl)-6-methoxygambogic acid methyl ester 

Relevant articles and documents

Caged garcinia xanthones, a novel chemical scaffold with potent antimalarial activity

Caged Garcinia xanthones (CGXs) constitute a family of natural products that are produced by tropical/subtropical trees of the genus Garcinia. CGXs have a unique chemical architecture, defined by the presence of a caged scaffold at the C ring of a xanthone moiety, and exhibit a broad range of biological activities. Here we show that synthetic CGXs exhibit antimalarial activity against Plasmodium falciparum, the causative parasite of human malaria, at the intraerythrocytic stages. Their activity can be substantially improved by attaching a triphenylphosphonium group at the A ring of the caged xanthone. Specifically, CR135 and CR142 were found to be highly effective antimalarial inhibitors, with 50% effective concentrations as low as 10 nM. CGXs affect malaria parasites at multiple intraerythrocytic stages, with mature stages (trophozoites and schizonts) being more vulnerable than immature rings. Within hours of CGX treatment, malaria parasites display distinct morphological changes, significant reduction of parasitemia (the percentage of infected red blood cells), and aberrant mitochondrial fragmentation. CGXs do not, however, target the mitochondrial electron transport chain, the target of the drug atovaquone and several preclinical candidates. CGXs are cytotoxic to human HEK293 cells at the low micromolar level, which results in a therapeutic window of around 150-fold for the lead compounds. In summary, we show that CGXs are potent antimalarial compounds with structures distinct from those of previously reported antimalarial inhibitors. Our results highlight the potential to further develop Garcinia natural product derivatives as novel antimalarial agents.