- Probing simple structural modification of α-mangostin on its cholinesterase inhibition and cytotoxicity
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α-Mangostin has been reported to possess a broad range of pharmacological effects including potent cholinesterase inhibition, but the development of α-mangostin as a potential lead compound is impeded by its toxicity. The present study investigated the impact of simple structural modification of α-mangostin on its cholinesterase inhibitory activities and toxicity toward neuroblastoma and liver cancer cells. The dialkylated derivatives retained good acetylcholinesterase (AChE) inhibitory activities with IC50 values between 4.15 and 6.73 μM, but not butyrylcholinesterase (BChE) inhibitory activities, compared with α-mangostin, a dual inhibitor (IC50: AChE, 2.48 μM; BChE, 5.87 μM). Dialkylation of α-mangostin produced AChE selective inhibitors that formed hydrophobic interactions at the active site of AChE. Interestingly, all four dialkylated derivatives of α-mangostin showed much lower cytotoxicity, being 6.4- to 9.0-fold and 3.8- to 5.5-fold less toxic than their parent compound on neuroblastoma and liver cancer cells, respectively. Likewise, their selectivity index was higher by 1.9- to 4.4-fold; in particular, A2 and A4 showed improved selectivity index compared with α-mangostin. Taken together, modification of the hydroxyl groups of α-mangostin at positions C-3 and C-6 greatly influenced its BChE inhibitory and cytotoxic but not its AChE inhibitory activities. These dialkylated derivatives are viable candidates for further structural modification and refinement, worthy in the search of new AChE inhibitors with higher safety margins.
- Khaw, Kooi-Yeong,Kumar, Pravin,Yusof, Siti Rafidah,Ramanathan, Surash,Murugaiyah, Vikneswaran
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- Acetyl- and O-alkyl- derivatives of β-mangostin from Garcinia mangostana and their anti-inflammatory activities
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Pure β-mangostin (1) was isolated from the stem bark of Garcinia mangostana L. One monoacetate (2) and five O-alkylated β-mangostin derivatives (3–7) were synthesised from β-mangostin. The structures of these compounds were elucidated and determined using spectroscopic techniques such as 1D NMR and MS. The cytotoxicities and anti-inflammatory activities of these five compounds against RAW cell 264.7 were tested. The structural-activity relationship studies indicated that β-mangostin showed a significant activity against the LPS-induced RAW cell 264.7, while the acetyl- as well as the O-alkyl- β-mangostin derivatives did not give good activity. Naturally occurring β-mangostin demonstrated comparatively better anti-inflammatory activity than its synthetic counterparts.
- Karunakaran, Thiruventhan,Ee, Gwendoline Cheng Lian,Ismail, Intan Safinar,Mohd Nor, Siti Mariam,Zamakshshari, Nor Hisam
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- Modified tetra-oxygenated xanthones analogues as anti-MRSA and P. aeruginosa agent and their synergism with vancomycin
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Five isolated xanthones from the C. cochinchinense and G. mangostana were evaluated and tested for antibacterial activities. Isolated 4 and 5 exhibited potent anti-MRSA and P. aeruginosa activity, but showed poor pharmacokinetic properties via ADMET prediction. It led us to improve pharmacokinetic properties of 4 and 5 by partially modifying them in acidic condition yielding fourteen analogues. It was found that analogues 4b, 4d and 5b possessed proper pharmacokinetic properties, while only 4b exhibited the best anti-MRSA and P. aeruginosa activity. The SEM results indicated that 4b may interact with or damage the cell wall of MRSA and P. aeruginosa. Moreover, a combination of 4b and vancomycin exhibits synergistic effect against both MRSA and P. aeruginosa at MIC value of 4.98 (MIC = 18.75 μg/mL for 4b) and 9.52 μg/mL (MIC = 75 μg/mL for 4b), respectively.
- Boonnak, Nawong,Chantrapromma, Suchada,Kaewpiboon, Chutima,Sathirakul, Korbtham
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supporting information
(2020/08/21)
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- Design, synthesis and structure-activity relationships of mangostin analogs as cytotoxic agents
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In order to better understand the structure-activity relationship of mangostin, a series of xanthone derivatives based on α-mangostin were designed and synthesized. All the compounds were evaluated for their cytotoxicity against a panel of five human canc
- Chi, Xiao-Qian,Zi, Cheng-Ting,Li, Hong-Mei,Yang, Liu,Lv, Yong-Feng,Li, Jin-Yu,Hou, Bo,Ren, Fu-Cai,Hu, Jiang-Miao,Zhou, Jun
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p. 41377 - 41388
(2019/01/03)
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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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Paragraph 0028; 0029
(2017/04/22)
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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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- Chemistry of α-mangostin. Studies on the semisynthesis of minor xanthones from Garcinia mangostana
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α-Mangostin is the major prenylated xanthone from Garcinia mangostana and it has been used also in recent times as starting material for the semisynthetic preparation of various biologically active derivatives. Its structure is characterised by the presence of few functional groups amenable to chemical manipulations, but present in the molecule in multiple instances (three phenolic hydroxyl groups, two prenyl chains and two unsubstituted aromatic carbons). This study represents a first approach to the systematic investigation of the reactivity of α-mangostin and describes the semisynthesis of some minor xanthones isolated from G. mangostana.
- Morelli, Carlo F.,Biagiotti, Marco,Pappalardo, Valeria M.,Rabuffetti, Marco,Speranza, Giovanna
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supporting information
p. 750 - 755
(2015/12/24)
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- Potent activity against multidrug-resistant Mycobacterium tuberculosis of α-mangostin analogs
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A new series of mangostin analogs of natural α-mangostin from mangosteen was prepared and their antimycobacterial activity was evaluated in vitro against Mycobacterium tuberculosis H37Ra. The results showed that the monoalkyl tetrahydro α-mangostin analogs displayed increased antimycobacterial activity as compared with the lead natural xanthone, α-mangostin. Among the tested compounds, 6-methoxytetrahydro α-mangostin (16) exhibited the most potent antimycobacterial activity with minimum inhibitory concentration (MIC) of 0.78 μg/mL. The activity of the monoalkylated and monoacylated tetrahydro α-mangostins decreases as the length of carbon chain increases. The methyl ether analog was also active against the multidrug- resistant (MDR) strains with pronounced MICs of 0.78-1.56 μg/mL.
- Sudta, Pichit,Jiarawapi, Payung,Suksamrarn, Apichart,Hongmanee, Poonpilas,Suksamrarn, Sunit
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p. 194 - 203
(2013/04/10)
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- Cytotoxic and NF-κB inhibitory constituents of the stems of Cratoxylum cochinchinense and their semisynthetic analogues
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A new caged xanthone (1), a new prenylxanthone (2), seven known xanthones, and a known sterol glucoside were isolated from the stems of Cratoxylum cochinchinense, collected in Vietnam. Compounds 1 and 2 were determined structurally by analysis of their sp
- Ren, Yulin,Matthew, Susan,Lantvit, Daniel D.,Ninh, Tran Ngoc,Chai, Heebyung,Fuchs, James R.,Soejarto, Djaja D.,De Blanco, Esperanza J. Carcache,Swanson, Steven M.,Kinghorn, A. Douglas
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experimental part
p. 1117 - 1125
(2011/07/30)
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- Cytotoxic geranylated xanthones and O-alkylated derivatives of α-mangostin
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Two new geranylated xanthones, 6-O-methylcowanin (4) and oliverixanthone (5), along with five known compounds, cowanin, rubraxanthone, cowaxanthone, cowanol, and β-mangostin, have been isolated from the bark of Garcinia oliveri. For comparison of their bi
- Ha, Ly Dieu,Hansen, Poul Erik,Vang, Ole,Duus, Fritz,Pham, Hung Dinh,Nguyen, Lien-Hoa Dieu
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experimental part
p. 830 - 834
(2010/01/19)
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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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