- Discovery of α-mangostin as a novel competitive inhibitor against mutant isocitrate dehydrogenase-1
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Somatic heterozygous mutations of isocitrate dehydrogenase-1 (IDH1) are abundantly found in several types of cancer and strongly implicate altered metabolism in carcinogenesis. In the present study, we have identified α-mangostin as a novel selective inhibitor of mutant IDH1 (IDH1-R132H). We have observed that α-mangostin competitively inhibits the binding of α-ketoglutarate (α-KG) to IDH1-R132H. The structure-relationship study reveals that α-mangostin exhibits the strongest core inhibitor structure. Finally, we have observed that α-mangostin selectively promotes demethylation of 5-methylcytosine (5mC) and histone H3 trimethylated lysine residues in IDH1 (+/R132H) MCF10A cells, presumably via restoring the activity of cellular α-KG-dependent DNA hydroxylases and histone H3 lysine demethylases. Collectively, we provide evidence that α-mangostin selectively inhibits IDH1-R132H.
- Kim, Hyo-Joon,Fei, Xiang,Cho, Seok-Cheol,Choi, Bu Young,Ahn, Hee-Chul,Lee, Kyeong,Seo, Seung-Yong,Keum, Young-Sam
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- A preparing method and uses of mangostin and mangostin analogues
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The invention belongs to the fields of innovative medicines and cosmetics and particularly relates to a preparing method and uses of mangostin shown as a formula (I) and mangostin analogues shown as a formula (II). Alpha-mangostin, beta-mangostin, gamma-mangostin and analogues thereof are respectively prepared through olefination and through controlling conditions for deprotection. According to the method, products are high in purity, operation is simple and convenient, yields are high, costs are low and the method is suitable for large-scale production. On one hand, the beta-mangostin, the gamma-mangostin, beta-methoxy-mangostin, and analogues thereof have ultraviolet absorption ability and ultraviolet light radiation preventing functions so that the beta-mangostin, the gamma-mangostin, the beta-methoxy-mangostin, and the analogues thereof can be adopted as a sun-screening agent separately or compounded with other sun-screening agents and applied into cosmetics; and on the other hand, the beta-mangostin, the gamma-mangostin, the beta-methoxy-mangostin, and the analogues thereof have activity of inhibiting acid sphingomyelinase so that the beta-mangostin, the gamma-mangostin, the beta-methoxy-mangostin, and the analogues thereof can be adopted as acid sphingomyelinase inhibitors and applied for preparation of medicines for preventing and treating acid sphingomyelinase related diseases mainly including cardio cerebrovascular diseases, neurological diseases, liver diseases, lung diseases, autoimmune diseases, infectious diseases and the like.
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- Mangostin the whole synthetic method
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The invention belongs to the field of chemical synthesis and particularly relates to a novel synthesis method of mangostin as shown in the formula (I), wherein the mangostin as a natural effective component has favorable anti-tumor activity, cardiovascular activity, antioxidant activity, anti-inflammatory activity, antibacterial activity and other pharmacological activities. The novel synthesis method comprises the steps: with 1, 7-dihydroxyl-3, 6-dialkoxyl-9H-xanthenone as a raw material, sequentially carrying out nucleophilic substitution, Claisen rearrangement, alkylation, deprotection and the like to obtain alpha-mangostin, beta-mangostin, belt-mangostin-OMe and gamma-mangostin. The novel synthesis method is simple in step and suitable for industrial production.
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- Novel Xanthone Derivatives and Composition for Treating Cancer Comprising the Same as Active Ingredient
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The present invention relates to a novel xanthone derivative compound, and an anticancer composition comprising the compound as an active ingredient. The xanthone derivative compound of the present invention exhibits excellent anticancer activities against various human cancer cells and remarkably enhanced water solubility compared to an alpha-mangostin compound which is a parent compound. Therefore, the xanthone derivative compound of the present invention can be developed into anticancer drugs having excellent activities.COPYRIGHT KIPO 2016
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- Synthesis of xanthone derivatives based on α-mangostin and their biological evaluation for anti-cancer agents
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A xanthone-derived natural product, α-mangostin is isolated from various parts of the mangosteen, Garcinia mangostana L. (Clusiaceae), a well-known tropical fruit. Novel xanthone derivatives based on α-mangostin were synthesized and evaluated as anti-cancer agents by cytotoxicity activity screening using 5 human cancer cell lines. Some of these analogs had potent to moderate inhibitory activities. The structure-activity relationship studies revealed that phenol groups on C3 and C6 are critical to anti-proliferative activity and C4 modification is capable to improve both anti-cancer activity and drug-like properties. Our findings provide new possibilities for further explorations to improve potency.
- Fei, Xiang,Jo, Minmi,Lee, Bit,Han, Sang-Bae,Lee, Kiho,Jung, Jae-Kyung,Seo, Seung-Yong,Kwak, Young-Shin
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p. 2062 - 2065
(2014/05/06)
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- Synthesis of the Mangostins
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Acylation of 5,7-bisbenzyloxy-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran (10c) with 6,8-dimethoxy-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-5-carboxylic acid (9b) in the presence of trifluoroacetic anhydride gave 5,7-dibenzyloxy-3,4-dihydro-2,2-dimethyl-2H-1
- Lee, Hiok-Huang
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p. 3205 - 3213
(2007/10/02)
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