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1.
Fitoterapia ; 175: 105952, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38614405

RESUMEN

Three new xanthone derivatives irpexols A-C (1-3) and five known xanthones including three dimeric ones were successfully isolated from Irpex laceratus A878, an endophytic fungus of the family Irpicaceae from the medicinal plant Pogostemon cablin (Blanco) Bentham (Lamiaceae). The structures of these compounds were elucidated by extensive spectroscopic analyses including ultraviolet-visible spectroscopy (UV), infrared spectroscopy (IR), mass spectrometry (MS), and nuclear magnetic resonance (NMR). All of the three new compounds (1-3) share a de-aromatic and highly­oxygenated xanthone skeleton. In addition, the cytotoxic activity of compounds 1-8 were evaluated against SF-268, MCF-7, HepG2, and A549 tumor cell lines. The results revealed that compound 6 showed moderate cytotoxic activity with the IC50 values ranging from 24.83 to 45.46 µM, while the IC50 values of the positive control adriamycin was ranging from 1.11 to 1.44 µM.


Asunto(s)
Endófitos , Xantonas , Xantonas/aislamiento & purificación , Xantonas/farmacología , Xantonas/química , Estructura Molecular , Humanos , Endófitos/química , Línea Celular Tumoral , Pogostemon/química , Antineoplásicos/farmacología , Antineoplásicos/aislamiento & purificación , Antineoplásicos/química , China
2.
Nat Prod Res ; 38(5): 885-890, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37029625

RESUMEN

This report describes the isolation and characterization of xanthones from Garcinia bancana Miq. and evaluates their antiplasmodial and anticancer activities. Macluraxanthone (1), isojacareubin (2), and gerontoxanthone C (3) were isolated from the stem bark of G. bancana Miq. for the first time. In silico molecular docking studies revealed the hydrogen bonding and steric interactions between xanthones (1-3) and PfLDH/VEGFR2. The in vitro antiplasmodial activity was assayed against the chloroquine-sensitive Plasmodium falciparum strain 3D7 by the lactate dehydrogenase (LDH) method. The anticancer evaluation was evaluated against the A549, MCF-7, HeLa, and B-16 cancer cell lines. Compounds (1) (IC50 8.45-16.71 µM) and (3) (IC50 9.69-14.86 µM) showed more potent anticancer activity than compound (2) (IC50 25.46-31.31 µM), as well for their antiplasmodial activity (4.28 µM, 5.52 µM, 11.45 µM). Our findings indicated the potential of G. bancana Miq. as a natural resource of antiplasmodial and anticancer compounds.


Asunto(s)
Antimaláricos , Garcinia , Xantonas , Antimaláricos/farmacología , Xantonas/farmacología , Simulación del Acoplamiento Molecular , Cloroquina , Plasmodium falciparum , Extractos Vegetales
3.
Fitoterapia ; 172: 105779, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38104910

RESUMEN

Six new compounds, including two depsidones garciculendepsidones A and B (1 and 2), one prenylated xanthone garciculenxanthone (3) and three dimeric xanthones bigarciculenxanthones A-C (4-6), were isolated from the twigs and leaves of Garcinia esculenta Y. H. Li. Their structures were elucidated based on comprehensive analyses of spectral data, including HRESIMS, 1D and 2D NMR, and ECD calculation. All the isolates were tested for their cytotoxicity against five human cancer cell lines (myeloid leukemia HL-60, lung cancer A-549 cells, hepatocellular carcinoma SMMC-7721, breast cancer MDA-MB-231 and colon cancer SW480), among them, compounds 3-5 displayed cytotoxic potential, especially garciculenxanthone (3) had the lowest IC50 value of 8.2 µm for lung cancer A-549 cells.


Asunto(s)
Antineoplásicos Fitogénicos , Antineoplásicos , Depsidos , Garcinia , Lactonas , Neoplasias Pulmonares , Xantonas , Humanos , Estructura Molecular , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Garcinia/química , Xantonas/farmacología , Xantonas/química , Neoplasias Pulmonares/tratamiento farmacológico
4.
Zhongguo Zhong Yao Za Zhi ; 48(21): 5817-5821, 2023 Nov.
Artículo en Chino | MEDLINE | ID: mdl-38114177

RESUMEN

Eight compounds were isolated from ethyl acetate fraction of 80% ethanol extract of the hulls of Garcinia mangostana by silica gel, Sephadex LH-20 column chromatography, as well as prep-HPLC methods. By HR-ESI-MS, MS, 1D and 2D NMR spectral analyses, the structures of the eight compounds were identified as 16-en mangostenone E(1), α-mangostin(2), 1,7-dihydroxy-2-(3-methy-lbut-2-enyl)-3-methoxyxanthone(3), cratoxyxanthone(4), 2,6-dimethoxy-para-benzoquinone(5), methyl orselinate(6), ficusol(7), and 4-(4-carboxy-2-methoxyphenoxy)-3,5-dimethoxybenzoic acid(8). Compound 1 was a new xanthone, and compound 4 was a xanthone dimer, compound 5 was a naphthoquinone. All compounds were isolated from this plant for the first time except compounds 2 and 3. Cytotoxic bioassay suggested that compounds 1, 2 and 4 possessed moderate cytotoxicity, suppressing HeLa cell line with IC_(50) va-lues of 24.3, 35.5 and 17.1 µmol·L~(-1), respectively. Compound 4 also could suppress K562 cells with an IC_(50) value of 39.8 µmol·L~(-1).


Asunto(s)
Antineoplásicos , Garcinia mangostana , Garcinia , Xantonas , Humanos , Garcinia mangostana/química , Células HeLa , Espectroscopía de Resonancia Magnética , Xantonas/farmacología , Garcinia/química , Extractos Vegetales/química , Estructura Molecular
5.
Cancers (Basel) ; 15(16)2023 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-37627222

RESUMEN

Mangiferin (MGF), a xanthone derived from Mangifera indica L., initially employed as a nutraceutical, is now being explored extensively for its anticancer potential. Scientists across the globe have explored this bioactive for managing a variety of cancers using validated in vitro and in vivo models. The in vitro anticancer potential of this biomolecule on well-established breast cancer cell lines such as MDA-MB-23, BEAS-2B cells and MCF-7 is closer to many approved synthetic anticancer agents. However, the solubility and bioavailability of this xanthone are the main challenges, and its oral bioavailability is reported to be less than 2%, and its aqueous solubility is also 0.111 mg/mL. Nano-drug delivery systems have attempted to deliver the drugs at the desired site at a desired rate in desired amounts. Many researchers have explored various nanotechnology-based approaches to provide effective and safe delivery of mangiferin for cancer therapy. Nanoparticles were used as carriers to encapsulate mangiferin, protecting it from degradation and facilitating its delivery to cancer cells. They have attempted to enhance the bioavailability, safety and efficacy of this very bioactive using drug delivery approaches. The present review focuses on the origin and structure elucidation of mangiferin and its derivatives and the benefits of this bioactive. The review also offers insight into the delivery-related challenges of mangiferin and its applications in nanosized forms against cancer. The use of a relatively new deep-learning approach to solve the pharmacokinetic issues of this bioactive has also been discussed. The review also critically analyzes the future hope for mangiferin as a therapeutic agent for cancer management.

6.
J Pharm Pharmacol ; 75(10): 1259-1293, 2023 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-37590382

RESUMEN

OBJECTIVES: The genus Cratoxylum contained medicinal herbs, which are widely distributed in South-East Asia and China. Plants of this genus were consumed as a vegetable side dish, a spice, an ingredient in soup, or a substitute for tea, as well as they are traditionally appropriate for various diseases such as fever, cough, flu, diarrhoea, etc. The most aims of the current review are to highlight the ultimate information about the traditional use, phytochemistry and pharmacology of Cratoxylum medicinal plants. KEY FINDINGS: The relevant literature data of Cratoxylum species have been gathered from Google Scholar, Sci-Finder, Web of Science, Science Direct and various journal websites. The most meaningful keyword 'Cratoxylum' was used in combination or alone in the search for references. SUMMARY: More than 150 reports have been retrieved from the search, completely written in English. Most of them are phytochemical and pharmacological studies, which determined the isolations of 277 metabolites. Xanthone derivatives (205 compounds, 74%) are essential, followed by other chemical classes such as flavonoids, anthraquinones, triterpenoids, benzophenones, phytosterols and tocopherols. Cratoxylum constituents possessed complexed pharmacological activities, including antioxidant, antibacterial, anti-inflammatory, antidiabetic, antihypertensive, antimalarial, antiviral, antiamoebic, protein tyrosine phosphatase 1B inhibitory, neuroprotective, hepatoprotective and gastroprotective activities, especially in terms of anticancer.

7.
Molecules ; 28(13)2023 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-37446849

RESUMEN

ACE2 and Mpro in the pathology of SARS-CoV-2 show great potential in developing COVID-19 drugs as therapeutic targets, due to their roles as the "gate" of viral entry and viral reproduction. Of the many potential compounds for ACE2 and Mpro inhibition, α-mangostin is a promising candidate. Unfortunately, the potential of α-mangostin as a secondary metabolite with the anti-SARS-CoV-2 activity is hindered due to its low solubility in water. Other xanthone isolates, which also possess the xanthone core structure like α-mangostin, are predicted to be potential alternatives to α-mangostin in COVID-19 treatment, addressing the low drug-likeness of α-mangostin. This study aims to assess the potential of xanthone derivative compounds in the pericarp of mangosteen (Garcinia mangostana L.) through computational study. The study was conducted through screening activity using molecular docking study, drug-likeness prediction using Lipinski's rule of five filtration, pharmacokinetic and toxicity prediction to evaluate the safety profile, and molecular dynamic study to evaluate the stability of formed interactions. The research results showed that there were 11 compounds with high potential to inhibit ACE2 and 12 compounds to inhibit Mpro. However, only garcinone B, in addition to being indicated as active, also possesses a drug-likeness, pharmacokinetic, and toxicity profile that was suitable. The molecular dynamic study exhibited proper stability interaction between garcinone B with ACE2 and Mpro. Therefore, garcinone B, as a xanthone derivative isolate compound, has promising potential for further study as a COVID-19 treatment as an ACE2 and Mpro inhibitor.


Asunto(s)
COVID-19 , Garcinia mangostana , Xantonas , Humanos , Garcinia mangostana/química , Enzima Convertidora de Angiotensina 2 , Simulación del Acoplamiento Molecular , Tratamiento Farmacológico de COVID-19 , SARS-CoV-2 , Xantonas/farmacología , Xantonas/uso terapéutico , Xantonas/química
8.
Fitoterapia ; 168: 105539, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37178810

RESUMEN

Phytochemical study on the whole plants of a Gentianaceous medicinal plant, Canscora lucidissima, gave one new acylated iridoid glucoside, canscorin A (1), and two new xanthone glycosides (2 and 3) together with 17 known compounds including five xanthones, eight xanthone glycosides, two benzophenone glucosides, caffeic acid, and loganic acid. Canscorin A (1) was assigned as a loganic acid derivative having a hydroxyterephthalic acid moiety by spectroscopic analysis together with chemical evidence, while 2 and 3 were elucidated to be a rutinosylxanthone and a glucosylxanthone, respectively. The absolute configurations of the sugar moieties of 2 and 3 were determined by HPLC analysis. The isolated compounds were evaluated for their inhibitory activities against erastin-induced ferroptosis on human hepatoma Hep3B cells and LPS-stimulated IL-1ß production from murine microglial cells.


Asunto(s)
Ferroptosis , Gentianaceae , Xantonas , Ratones , Humanos , Animales , Glucósidos Iridoides , Estructura Molecular , Glicósidos/farmacología , Glicósidos/química , Xantonas/farmacología
9.
Int J Mol Sci ; 24(4)2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36835343

RESUMEN

Mangosteen peel, a waste produced during mangosteen processing, has been reported to be rich in xanthone and anthocyanin, both of which possess vital biological activities such as anti-cancer properties. The objectives of this study were to analyze various xanthones and anthocyanins in mangosteen peel by UPLC-MS/MS for the subsequent preparation of both xanthone and anthocyanin nanoemulsions to study their inhibition effects on liver cancer cells HepG2. Results showed that methanol was the optimal solvent for the extraction of xanthones and anthocyanins, with a total amount of 68,543.39 and 2909.57 µg/g, respectively. A total of seven xanthones, including garcinone C (513.06 µg/g), garcinone D (469.82 µg/g), γ-mangostin (11,100.72 µg/g), 8-desoxygartanin (1490.61 µg/g), gartanin (2398.96 µg/g), α-mangostin (51,062.21 µg/g) and ß-mangostin (1508.01 µg/g), as well as two anthocyanins including cyanidin-3-sophoroside (2889.95 µg/g) and cyanidin-3-glucoside (19.72 µg/g), were present in mangosteen peel. The xanthone nanoemulsion was prepared by mixing an appropriate portion of soybean oil, CITREM, Tween 80 and deionized water, while the anthocyanin nanoemulsion composed of soybean oil, ethanol, PEG400, lecithin, Tween 80, glycerol and deionized water was prepared as well. The mean particle size of the xanthone extract and nanoemulsion were, respectively, 22.1 and 14.0 nm as determined by DLS, while the zeta potential was -87.7 and -61.5 mV. Comparatively, xanthone nanoemulsion was more effective than xanthone extract in inhibiting the growth of HepG2 cells, with the IC50 being 5.78 µg/mL for the former and 6.23 µg/mL for the latter. However, the anthocyanin nanoemulsion failed to inhibit growth of HepG2 cells. Cell cycle analysis revealed that the proportion of the sub-G1 phase followed a dose-dependent increase, while that of the G0/G1 phase showed a dose-dependent decline for both xanthone extracts and nanoemulsions, with the cell cycle being possibly arrested at the S phase. The proportion of late apoptosis cells also followed a dose-dependent rise for both xanthone extracts and nanoemulsions, with the latter resulting in a much higher proportion at the same dose. Similarly, the activities of caspase-3, caspase-8 and caspase-9 followed a dose-dependent increase for both xanthone extracts and nanoemulsions, with the latter exhibiting a higher activity at the same dose. Collectively, xanthone nanoemulsion was more effective than xanthone extract in inhibiting the growth of HepG2 cells. Further research is needed to study the anti-tumor effect in vivo.


Asunto(s)
Garcinia mangostana , Neoplasias Hepáticas , Xantonas , Humanos , Antocianinas , Espectrometría de Masas en Tándem , Aceite de Soja , Cromatografía Liquida , Polisorbatos , Xantonas/farmacología , Línea Celular Tumoral , Extractos Vegetales/farmacología , Agua
10.
J Nat Med ; 77(2): 403-411, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36746835

RESUMEN

In the continuing discovery and structure elucidation of natural xanthone dimers, which are still rarely reported in absolute configuration, three new xanthone dimers, eumitrins I-K (1-3) were isolated from the lichen Usnea baileyi, a rich source of natural xanthone dimers. Their structures were elucidated unambiguously by spectroscopic analyses, including high-resolution electrospray ionization mass spectrometry (HRESIMS), 1D and 2D nuclear magnetic resonance spectroscopy (1D and 2D NMR). The absolute configuration of all three compounds was established through DP4 probability and ECD calculation. All compounds revealed weak activity for their enzymatic inhibition against α-glucosidase and tyrosinase, as well as antibacterial activity.


Asunto(s)
Líquenes , Xantonas , Estructura Molecular , Xantonas/química
11.
Chem Biodivers ; 20(2): e202200910, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36628555

RESUMEN

Garcinia cowa of the Clusiaceae family, native to South-East Asia used in traditional medicine. It has antipyretic, antimicrobial, and many other biological activities. In this review, a thorough study of this plant's chemical constituents and pharmacological and therapeutic effects was conducted from the research articles from PubMed, Science Direct, Google Scholar, and Scopus from 1977 to 2022. Reported secondary metabolites are enriched with xanthones, phloroglucinols, depsidones, steroids, etc. α-mangostin, ß-mangostin, cowaxanthone, rubraxanthone, cowanin, norcowanin, etc. represent the major xanthones. This article discusses the relationship between the different functional groups in xanthone compounds and their bioactivity against cancer, diabetes, bacteria, leishmania, malaria, and inflammation. This review is a comprehensive compendium of major bioactive molecules and its implication for human disease.


Asunto(s)
Garcinia , Xantonas , Humanos , Garcinia/química , Fitoquímicos , Extractos Vegetales/química , Xantonas/química
12.
J Ethnopharmacol ; 306: 116130, 2023 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-36621661

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Garcinia oligantha Merr. is an ethnomedicine plant mainly distributed in Guangdong and Hainan, China. It has the effects of heat-clearing and detoxicating, which has been used by local ethnic minorities to treat a variety of diseases, including inflammation, internal heat, toothache and scald. THE AIM OF THE REVIEW: This review summarizes and discusses the progress of the chemical compounds and biological activities of G. oligantha that have been studied in recent years to provide the direction for the prospective research and applications of G. oligantha. MATERIALS AND METHODS: The relevant literature about G. oligantha was accessible from ancient Chinese medical books and records, theses, as well as major scientific databases such as Google Scholar, PubMed, Web of Science, ScienceDirect, SciFinder, Baidu Scholar and China National Knowledge Infrastructure (CNKI). RESULTS: To date, more than 150 chemical compounds were isolated from this plant, including xanthones, volatile oil, fatty acid, benzofurane derivative and biphenyl compounds. Xanthones are the main bioactive compounds that exhibit diverse biological effects, such as antitumor, analgesic, anti-inflammatory, antioxidative, neuroprotective, antimalarial and antibacterial effects, which are consistent with its traditional uses as a folk medicine. Modern pharmacological studies show that these compounds participate in a variety of signaling pathways underlying different pathophysiologies, making them a valuable medicinal resource. CONCLUSION: G. oligantha is an ethnomedicine with a long history. However, due to regional and cultural constraints, the popularisation and use of ethnomedicine are still limited. Modern pharmacological and chemical research suggest that G. oligantha contains a variety of bioactive compounds and showed diverse biological functions, which is worthy of comprehensive and in-depth research. This review summarizes and discusses the recent progress in studies on G. oligantha, looking forward to promote further research and sustainable development of folk medicinal plants.


Asunto(s)
Garcinia , Xantonas , Etnofarmacología , Estudios Prospectivos , Fitoquímicos/farmacología , Medicina Tradicional , Extractos Vegetales/farmacología , Medicina Tradicional China
13.
Nat Prod Res ; 37(5): 702-712, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35695129

RESUMEN

A new geranylated xanthone, nigrolineaxanthone AA (1) together with 18 known compounds (2-19) were isolated from latex and twig extracts of Garcinia nigrolineata Planch. ex T. Anderson. Some of the isolated compounds were assessed for their antidiabetic activities and cytotoxicity against three cancer cell lines. Of these, compounds 12 (IC50 value of 25.8 ± 0.2 µM), 16 (IC50 value of 124.8 ± 0.7 µM), and 17 (IC50 value of 44.4 ± 1.1 µM) exhibited the highest α-glucosidase inhibitory, α-amylase inhibitory, and glycation inhibition activities, respectively. Compound 11 showed glucose consumption and glucose uptake with IC50 values of 14.2 ± 0.8 µM and 3.1-fold. Compound 10 displayed cytotoxic activity against colon cancer (SW480) with an IC50 value of 4.3 ± 0.1 µM), while compound 2 showed cytotoxicity against leukemic cancer (K562) with IC50 value of 4.4 ± 0.3 µM.


Asunto(s)
Antineoplásicos , Clusiaceae , Garcinia , Xantonas , Látex , Hipoglucemiantes/farmacología , Estructura Molecular , Extractos Vegetales/farmacología , Xantonas/farmacología
14.
Chem Biodivers ; 20(1): e202200900, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36404281

RESUMEN

Four new xanthone glucosides, 3-hydroxy-2-methoxyxanthone-4-O-ß-D-glucopyranoside (1), 4,8-dihydroxy-2-methoxyxanthone-3-O-ß-D-glucopyranoside (2), 2-methoxyxanthone-5-O-ß-D-glucopyranoside (3), 4-hydroxy-2-methoxyxanthone-3-O-ß-D-glucopyranoside (4), a new phenolic acid, 4,4'-dihydroxy-3,3'-imino-di-benzoic acid monomethyl ester (5), and a new isoquinoline, methyl 6-hydroxy-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate (6) were isolated from the fruit of Hypericum patulum. The structural elucidation of the isolated compounds was primarily based on HR-ESI-MS, UV, IR, 1D and 2D NMR. All compounds were evaluated for their inhibitory effect against LPS-induced NO production in RAW 264.7 cells. Compound 2, 3 exhibited moderate inhibitory activity against NO production.


Asunto(s)
Hypericum , Hypericum/química , Frutas/química , Glucósidos/química , Espectroscopía de Resonancia Magnética
15.
Nat Prod Res ; 37(9): 1480-1490, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-34984944

RESUMEN

The lichen Usnea baileyi is a fruticose lichen belonging to the Usnea genus. It is well known as a rich source of natural xanthone dimers and possesses various bioactivities. Nevertheless, the chemical investigation on this type of lichen is still rare as most of researches reported its components without structural elucidation. Herein, in the continuous study on this type of lichen, we further isolate xanthone dimers from the dichloromethane extract and explore three new xanthone dimers, eumitrins F - H (1 - 3). Their structures were elucidated unambiguously by spectroscopic analyses, including high resolution electrospray ionisation mass spectrometry (HRESIMS), 1 D and 2 D nuclear magnetic resonance spectroscopy (1 D and 2 D NMR), and DP4 probability. All compounds were evaluated for their enzyme inhibition against α-glucosidase, tyrosinase, and antibacterial activity. They revealed moderate antimicrobial and weak tyrosinase inhibition. For α-glucosidase inhibition, compound 3 displayed the most significant inhibitory against α-glucosidase possessing an IC50 value of 64.2 µM.


Asunto(s)
Líquenes , Usnea , Xantonas , alfa-Glucosidasas , Monofenol Monooxigenasa , Usnea/química , Xantonas/química , Hidrógeno/química , Flúor/química
16.
Zhongguo Zhong Yao Za Zhi ; 47(20): 5544-5549, 2022 Oct.
Artículo en Chino | MEDLINE | ID: mdl-36471971

RESUMEN

Repeated silica gel column chromatography, reversed-phase C_(18) column chromatography, Sephadex LH-20 column chromatography, high performance liquid chromatography and semi-preparative medium pressure liquid chromatography were performed to separate and purify the chemical constituents of Hypericum lagarocladum. Spectroscopic methods such as mass spectrometry(MS) and nuclear magnetic resonance(NMR) combined with physicochemical properties were adopted in identifying the structure of the isolated compounds. Ten compounds were isolated from the ethyl acetate fraction of H. lagarocladum and identified as lagarxanthone A(1), 1,7-dihydroxyxanthone(2), 3,4,5-trihydroxyxanthone(3), 2,7-dihydroxy-1-methoxyxanthone(4), 1,3-dihydroxy-7-methoxyxanthone(5), 1,5-dihydroxy-8-methoxyxanthone(6), 3,4-dihydroxy-2-methoxyxanthone(7), 3,4-dihydroxy-5-methoxyxanthone(8), 2,3-dimethoxyxanthone(9), and 2,3,4-trimethoxyxanthone(10). Among them, compound 1 was a new compound, and compounds 2-10 were isolated from this plant for the first time. These ten compounds were tested for glucose uptake in L6 cells, and the results showed that all the compounds had no significant effect on glucose uptake.


Asunto(s)
Hypericum , Xantonas , Hypericum/química , Cromatografía Líquida de Alta Presión , Espectroscopía de Resonancia Magnética , Glucosa
17.
BMC Complement Med Ther ; 22(1): 266, 2022 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-36224571

RESUMEN

BACKGROUND: The emergence of antimalarial drug resistance encourages the search for new antimalarial agents. Mammea siamensis belongs to the Calophyllaceae family, which is a medicinal plant that is used in traditional Thai preparations. The hexane and dichloromethane extracts of this plant were found to have potent antimalarial activity. Therefore, this study aimed to isolate active compounds from M. siamensis flowers and evaluate their antimalarial potential and their interactions with Plasmodium falciparum lactate dehydrogenase (PfLDH). METHODS: The compounds from M. siamensis flowers were isolated by chromatographic techniques and evaluated for their antimalarial activity against chloroquine (CQ)-resistant P. falciparum (K1) strains using a parasite lactate dehydrogenase (pLDH) assay. Interactions between the isolated compounds and the PfLDH enzyme were investigated using a molecular docking method. RESULTS: The isolation produced the following thirteen compounds: two terpenoids, lupeol (1) and a mixture of ß-sitosterol and stigmasterol (5); two mammea coumarins, mammea A/AA cyclo D (6) and mammea A/AA cyclo F (7); and nine xanthones, 4,5-dihydroxy-3-methoxyxanthone (2), 4-hydroxyxanthone (3), 1,7-dihydroxyxanthone (4), 1,6-dihydroxyxanthone (8), 1-hydroxy-5,6,7-trimethoxyxanthone (9), 3,4,5-trihydroxyxanthone (10), 5-hydroxy-1-methoxyxanthone (11), 2-hydroxyxanthone (12), and 1,5-dihydroxy-6-methoxyxanthone (13). Compound 9 exhibited the most potent antimalarial activity with an IC50 value of 9.57 µM, followed by 10, 1, 2 and 13 with IC50 values of 15.48, 18.78, 20.96 and 22.27 µM, respectively. The molecular docking results indicated that 9, which exhibited the most potent activity, also had the best binding affinity to the PfLDH enzyme in terms of its low binding energy (-7.35 kcal/mol) and formed interactions with ARG109, ASN140, and ARG171. CONCLUSION: These findings revealed that isolated compounds from M. siamensis flowers exhibited antimalarial activity. The result suggests that 1-hydroxy-5,6,7-trimethoxyxanthone is a possible lead structure as a potent inhibitor of the PfLDH enzyme.


Asunto(s)
Antimaláricos , Flores , Mammea , Extractos Vegetales , Antimaláricos/farmacología , Flores/química , Mammea/química , Simulación del Acoplamiento Molecular , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología
18.
Phytomedicine ; 102: 154118, 2022 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-35576741

RESUMEN

BACKGROUND: Nonsmall-cell lung cancer (NSCLC) is one of the most common malignant tumors, and the current drugs have not achieved ideal therapeutic effects. The abnormal activation of STAT3 and FAK signal transduction in tumor cells is highly correlated with their proliferation and migration ability. Therefore, bioactive compounds that can inhibit STAT3 and FAK activation have the potential to become agents to treat NSCLC. PURPOSE: This study aims to discover new antitumor compounds from Garcinia xipshuanbannaensis and investigate the molecular mechanism by which they inhibit lung cancer proliferation and metastasis in vivo and in vitro, all of which may lead to obtainment of a potential antitumor agent. METHODS: Xipsxanthone H was obtained by various chromatography methods (including silica gel, medium pressure liquid chromatography (MPLC), and preparative high-performance liquid chromatography (HPLC)). 1D and 2D nuclear magnetic resonance (NMR) spectra were used to analyze the structure. Cell viability and wound healing assays were employed to detect changes in the proliferation and migration of cancer cells. Cell cycle and apoptosis were analyzed by flow cytometry. The protein expression of STAT3 and FAK signaling pathways affected by xipsxanthone H was determined by Western blotting. The zebrafish model was used to evaluate the in vivo effects of xipshantone H on tumor proliferation and metastasis. Molecular docking was utilized to explore the interaction between xipsxanthone H and STAT3. Cellular thermal shift assays (CETSAs) were employed to explore the possible target of xipsxanthone H. RESULTS: The novel compound xipsxanthone H was purified and characterized from G. xipshuanbannaensis. Xipsxanthone H exhibited strong anti-proliferation activity in a variety of tumor cell lines. In addition to inducing reactive oxygen species (ROS) production and arresting the cell cycle, mechanistic studies demonstrated that xipsxanthone H suppressed STAT3 and FAK phosphorylation and regulated the downstream protein expression of the STAT3 and FAK signaling pathways. The in vivo studies using the zebrafish model revealed that xipsxanthone H inhibited tumor proliferation, metastasis, and angiogenesis. CONCLUSIONS: A new xanthone was obtained from G. xipshuanbannaensis, and this compound had the property of inhibiting tumor proliferation and metastasis by targeting STAT3 and FAK signaling pathways in NSCLC. These findings suggested that xipsxanthone H might be a potential candidate agent for NSCLC treatment.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Xantonas , Animales , Apoptosis , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias Pulmonares/patología , Simulación del Acoplamiento Molecular , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Xantonas/farmacología , Xantonas/uso terapéutico , Pez Cebra/metabolismo
19.
Molecules ; 27(9)2022 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-35565960

RESUMEN

A new xanthone glycoside, 1,3,5,6-tetrahydroxyxanthone-C-4-ß-d-glucopyranoside was isolated from the methanol extract of Mangifera indica leaves (Anacardiaceae) growing in Egypt. The structure was clarified by 1D and 2D-NMR spectroscopic data. The physicochemical properties of the compound such as lipophilicity, solubility, and formulation considerations were predicted via in silico ADMET technique using the SwissADME server. This technique provided Lipinski's rule of five, such as GIT absorption, distribution, metabolism, and skin permeation. The in vitro inhibitory activities against aging-mediated enzymes such as collagenase, elastase, hyaluronidase, and tyrosinase were assessed. The compound exhibited remarkable anti-collagenase, anti-elastase, anti-hyaluronidase, and anti-tyrosinase effects with IC50 values of 1.06, 419.10, 1.65, and 0.48 µg/mL, respectively, compared to the positive control. The compound showed promising predicted aqueous solubility and reasonable skin penetration suggesting the suitability of the compound for topical formulation as an anti-aging agent for cosmetic preparations.


Asunto(s)
Glicósidos Cardíacos , Mangifera , Envejecimiento de la Piel , Xantonas , Colagenasas/metabolismo , Glicósidos/farmacología , Hialuronoglucosaminidasa/metabolismo , Mangifera/metabolismo , Monofenol Monooxigenasa , Extractos Vegetales/química , Extractos Vegetales/farmacología , Xantonas/química , Xantonas/farmacología
20.
J Nat Med ; 75(4): 871-876, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33999337

RESUMEN

Four new xanthones, named schomburgones C-F (1‒4), along with six known xanthones (5‒10) were isolated from the stems of Garcinia schomburgkiana. Their structures were determined by spectroscopic analysis especially 1D and 2D NMR spectroscopies. The isolated compounds were evaluated for their cytotoxicity against five human cancer cell lines. Furanoxanthones 4‒6 showed potent cytotoxicity against four cell lines (KB, HeLa S3, MCF-7 and Hep G2) with IC50 values in the range of 0.18‒9.95 µM.


Asunto(s)
Antineoplásicos Fitogénicos , Garcinia , Xantonas , Antineoplásicos Fitogénicos/farmacología , Línea Celular , Humanos , Estructura Molecular , Xantonas/farmacología
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