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1.
Chem Pharm Bull (Tokyo) ; 70(12): 885-891, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36450587

RESUMO

A new coumarin derivative (1) and 30 known compounds were isolated from Mammea siamensis and Andrographis paniculata, guided by B cell-specific Moloney murine leukemia virus insertion region 1 (BMI1) promoter inhibitory activity. Among the isolated compounds, 15 compounds showed BMI1 promoter inhibitory activity, and five compounds were found to be cytotoxic. 14-Deoxy-11,12-dehydroandrographolide (18) was highly cytotoxic to DU145 cells with an IC50 value of 25.4 µM. Western blotting analysis of compound 18 in DU145 cells suggested that compound 18 suppresses BMI1 expression.


Assuntos
Mammea , Camundongos , Animais , Andrographis paniculata , Ácidos Tri-Iodobenzoicos , Linhagem Celular , Proteínas Proto-Oncogênicas , Complexo Repressor Polycomb 1
2.
Int J Mol Sci ; 23(19)2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36232534

RESUMO

With the aim of searching for phytochemicals with aromatase inhibitory activity, five new prenylcoumarins, mammeasins K (1), L (2), M (3), N (4), and O (5), were isolated from the methanolic extract of Mammea siamensis (Miq.) T. Anders. flowers (fam. Calophyllaceae), originating in Thailand. The stereostructures of 1-5 were elucidated based on their spectroscopic properties. Among the new compounds, 1 (IC50 = 7.6 µM) and 5 (9.1 µM) possessed relatively strong inhibitory activity against aromatase, which is a target of drugs already used in clinical practice for the treatment and prevention of estrogen-dependent breast cancer. The analysis through Lineweaver-Burk plots showed that they competitively inhibit aromatase (1, Ki = 3.4 µM and 5, 2.3 µM). Additionally, the most potent coumarin constituent, mammea B/AB cyclo D (31, Ki = 0.84 µM), had a competitive inhibitory activity equivalent to that of aminoglutethimide (0.84 µM), an aromatase inhibitor used in therapeutics.


Assuntos
Mammea , Plantas Medicinais , Aminoglutetimida , Aromatase , Inibidores da Aromatase/farmacologia , Cumarínicos/química , Cumarínicos/farmacologia , Estrogênios/farmacologia , Mammea/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Tailândia
3.
BMC Complement Med Ther ; 22(1): 266, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36224571

RESUMO

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.


Assuntos
Antimaláricos , Flores , Mammea , Extratos Vegetais , Antimaláricos/farmacologia , Flores/química , Mammea/química , Simulação de Acoplamento Molecular , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia
4.
Fitoterapia ; 148: 104780, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33246033

RESUMO

Geranylated coumarins named mammeasins G-J (1-4) were isolated from the methanol extract of the flowers of Mammea siamensis (Miq.) T. Anders. (Calophyllaceae) originating in Thailand. Their structures were established based on detailed spectroscopic analyses. The isolates, including previously reported coumarin constituents (5-28), exhibited anti-proliferative activities against human carcinoma cell lines HSC-2, HSC-4, MKN-45, and MCF-7. Mammeasin A (7, IC50 = 13.6 µM) and surangin B (15, 15.2 µM), both consisting of the geranyl group, were found to show relatively strong activities against HSC-4 cells and their mechanisms of action were found to involve apoptotic cell death.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Cumarínicos/farmacologia , Neoplasias Gastrointestinais/patologia , Mammea/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose , Carcinoma/tratamento farmacológico , Carcinoma/patologia , Linhagem Celular Tumoral , Cumarínicos/isolamento & purificação , Flores/química , Neoplasias Gastrointestinais/tratamento farmacológico , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Plantas Medicinais/química , Tailândia
5.
Bioorg Chem ; 100: 103894, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32388434

RESUMO

Chagas Disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi which affects 6-8 million people, mostly in Latin America. The medical treatment is based on two nitroimidazole compounds, which have limited effectiveness in the chronic phase of the disease and produce several adverse effects; consequently, there is an urgent need to develop new, safe, and effective drugs. Previous reports had shown that natural coumarins, especially mammea A/BA isolated from the tropical tree Calophyllum brasiliense, is a promissory molecule for developing new drugs, due to its potent activity, higher than benznidazole, selectivity, and its low toxicity in mice. However, its mode of action is still unknown. In the present work, we evaluated the mechanism of action of the coumarin mammea A/BA (93.6%), isolated from the tropical tree C. brasiliense on Querétaro strain (Tc1) of T. cruzi. This compound was tested in vitro on epimastigotes and trypomastigotes of T. cruzi for intracellular esterase activity, plasma membrane integrity, phosphatidylserine exposure, ROS production, mitochondrial membrane potential, caspase-like activity, DNA integrity, cell cycle and autophagy. Mammea A/BA showed a 50% lethal concentration (LC50) of 85.8 and 36.9 µM for epimastigotes and trypomastigotes respectively. It affected intracellular esterase activity, produced important plasma membrane damage and induced phosphatidylserine exposure. An increase in reactive oxygen species (ROS) and decrease in mitochondrial membrane potential were detected. Caspase-like activity was present in both parasite forms producing DNA integrity damage. This compound also induced a cell cycle arrest in the G1 phase and the presence of autophagy vacuoles. The above data suggest that mammea A/BA induce cell death of T. cruzi by autophagy and apoptosis-like phenomena and support our suggestion that mammea A/BA could be a promising molecule for the development of new drugs to treat Chagas Disease.


Assuntos
Calophyllum/química , Cumarínicos/química , Cumarínicos/farmacologia , Tripanossomicidas/química , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Humanos , Mammea/química , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Trypanosoma cruzi/citologia , Trypanosoma cruzi/metabolismo
6.
Biomedica ; 40(1): 55-71, 2020 03 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32220164

RESUMO

Introduction: Infectious diseases represent one of the leading causes of death worldwide. Considering the growing global challenge of antimicrobial resistance, research into new sources of potentially effective antimicrobial agents from natural origins is of great importance for world health. Objective: To evaluate the antimicrobial activity of endophytic fungi from Mammea americana and Moringa oleifera upon Staphylococcus aureus (ATCC 29213), S. aureus (resistant strain USb003), Escherichia coli (ATCC 25922), and E. coli (resistant strain USb007). Materials and methods: We isolated endophytic fungi from the leaves, seeds, and stems of the two plants under study. We evaluated their antimicrobial activity through the formation of sensitivity haloes in dual tests in vitro, as well as in trials using crude ethanolic extracts from the endophytes. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and cytotoxicity o the substances were analyzed. Results: Three ethanolic extracts of Penicillium sp., Cladosporium (001), and Cladosporium (002) exhibited the greatest inhibition halos in sensitive and resistant strains of E. coli and S. aureus. The MIC and CBM found were statistically significant (p≤0.05) compared with the gentamicin control. Furthermore, the cytotoxicity test results of CC50>1,000 demonstrated that the endophytic fungi studied exhibit bactericidal characteristics without causing unintended damage. Conclusion: The endophytic fungi M. oleifera and M. americana represent a source of active secondary metabolites with antimicrobial and non-toxic properties. In light of these findings, further research should proceed with chemical identification of the compounds and the study of their mechanisms of action, especially given the paucity of current scientific knowledge concerning the isolation of endophytes in these plants.


Introducción. Las enfermedades infecciosas son una causa importante de muertes en el mundo. La resistencia antimicrobiana es un problema global, por lo que es conveniente la investigación de nuevas fuentes de agentes antimicrobianos de origen natural potencialmente efectivos. Objetivo. Evaluar la actividad antimicrobiana de hongos endófitos de Mammea americana y Moringa oleifera en la cepa sensible (ATCC 29213) y en la cepa resistente (USb003) de Staphylococcus aureus, así como en la cepa sensible (ATCC 25922) y la cepa resistente (USb007) de Escherichia coli. Materiales y métodos. Se aislaron 14 hongos endófitos de las hojas, semillas y tallos de las dos plantas en estudio. Se evaluó su actividad antimicrobiana mediante la formación de halos de sensibilidad por ensayo dual in vitro y pruebas con extractos etanólicos crudos provenientes de los endófitos a los que se les evaluó la concentración mínima inhibitoria (CMI), la concentración bactericida mínima (CBM) y la citotoxicidad. Resultados. Tres extractos etanólicos de Penicillium sp., Cladosporium sp. (001) y Cladosporium sp. (002) presentaron mayores halos de inhibición en cepas sensibles y resistentes de E. coli y S. aureus. La CMI y la CBM halladas fueron estadísticamente significativas (p≤0,05), comparadas con el control de gentamicina. Las pruebas de citotoxicidad (concentración citotóxica, CC50>1.000) demostraron que los hongos endófitos poseen características bactericidas y no ocasionan daño alguno. Conclusión. Se halló una fuente de metabolitos secundarios activos con propiedades antimicrobianas y no tóxicas en los hongos endófitos de M. oleifera y M. americana; estos hallazgos son importantes para continuar con la identificación química de los compuestos y el estudio de sus mecanismos de acción en estas plantas en las que el aislamiento de endófitos ha sido escaso.


Assuntos
Antibacterianos/isolamento & purificação , Endófitos/fisiologia , Fungos/fisiologia , Mammea/microbiologia , Moringa oleifera/microbiologia , Plantas Medicinais/microbiologia , Animais , Antibacterianos/farmacologia , Chlorocebus aethiops , Cladosporium/química , Cladosporium/isolamento & purificação , Cladosporium/fisiologia , Avaliação Pré-Clínica de Medicamentos , Farmacorresistência Bacteriana Múltipla , Endófitos/isolamento & purificação , Escherichia coli/efeitos dos fármacos , Etanol , Fungos/isolamento & purificação , Testes de Sensibilidade Microbiana , Penicillium/química , Penicillium/isolamento & purificação , Penicillium/fisiologia , Folhas de Planta/microbiologia , Caules de Planta/microbiologia , Sementes/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Células Vero
7.
Molecules ; 25(2)2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31952109

RESUMO

The metabolite profiling associated with the antioxidant potential of Amazonian fruits represents an important step to the bioactive compound's characterization due to the large biodiversity in this region. The comprehensive bioactive compounds profile and antioxidant capacities of mamey apple (Mammea americana), camapu (Physalis angulata), and uxi (Endopleura uchi) was determined for the first time. Bioactive compounds were characterized by ultra-performance liquid chromatography coupled to high resolution mass spectrometry (UPLC-MSE) in aqueous and ethanolic extracts. Globally, a total of 293 metabolites were tentatively identified in mamey apple, campau, and uxi extracts. The main classes of compounds in the three species were terpenoids (61), phenolic acids (58), and flavonoids (53). Ethanolic extracts of fruits showed higher antioxidant activity and total ion abundance of bioactive compounds than aqueous. Uxi had the highest values of phenolic content (701.84 mg GAE/100 g), ABTS (1602.7 µmol Trolox g-1), and ORAC (15.04 µmol Trolox g-1). Mamey apple had the highest results for DPPH (1168.42 µmol TE g-1) and FRAP (1381.13 µmol FSE g-1). Nuclear magnetic resonance (NMR) spectroscopy results showed that sugars and lipids were the substances with the highest amounts in mamey apple and camapu. Data referring to chemical characteristics and antioxidant capacity of these fruits can contribute to their economic exploitation.


Assuntos
Antioxidantes/farmacologia , Frutas/metabolismo , Magnoliopsida/metabolismo , Mammea/metabolismo , Metaboloma/efeitos dos fármacos , Physalis/metabolismo , Cromatografia Líquida de Alta Pressão , Espectroscopia de Ressonância Magnética , Espectrometria de Massas em Tandem
8.
Artigo em Inglês | MEDLINE | ID: mdl-28573218

RESUMO

BACKGROUND: Saraphi (Mammea siamensis) is a Thai traditional herb. In this study, the cytotoxic effects of crude ethanolic and fractional extracts including hexane, ethyl acetate, and methanol fractions from M. siamensis flowers were investigated in order to determine their effect on WT1 expression in Molt4 and K562 cells and Bcr/Abl expression in K562 cells. MATERIALS AND METHODS: The flowers of M. siamensis were extracted using ethanol. The ethanol flower extract was further fractionated with hexane, ethyl acetate, and methanol. Cytotoxic effects were measured by the MTT assay. Bcr/Abl and WT1 protein levels after treatments were determined by Western blotting. The total cell number was determined via the typan blue exclusion method. RESULTS: The hexane fraction showed the strongest cytotoxic activity on Molt4 and K562 cells, with IC50 values of 2.6 and 77.6 µg/ml, respectively. The hexane extract decreased Bcr/Abl protein expression in K562 cells by 74.6% and WT1 protein expressions in Molt4 and K562 cells by 68.4 and 72.1%, respectively. Total cell numbers were decreased by 66.2 and 48.7% in Molt4 and K562 cells, respectively. Mammea E/BB (main active compound) significantly decreased both Bcr/Abl and WTlprotein expressions by 75 and 49.5%, respectively when compared to vehicle control. CONCLUSION: The hexane fraction from M. siamensis flowers inhibited cell proliferation via the suppression of WT1 expression in Molt4 and K562 cells and Bcr/Abl expression in K562 cells. The active compound may be mammea E/BB. Extracts from M. siamensis flowers show promise as naturally occurring anti-cancer drugs.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Proteínas de Fusão bcr-abl/metabolismo , Leucemia/tratamento farmacológico , Mammea , Fitoterapia , Extratos Vegetais/uso terapêutico , Proteínas WT1/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Proliferação de Células , Flores , Humanos , Células K562 , Leucemia/metabolismo , Medicina Tradicional , Proteínas Oncogênicas v-abl/metabolismo , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-bcr/metabolismo , Tailândia
9.
Food Chem ; 234: 269-275, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28551236

RESUMO

Our objective was to compare fruit morphology, physico-chemistry and bioactive compounds content of the edible pulp of six Mammea americana accessions. The results showed that this fruit was rather big, weighing on average 600 to 1100g depending on the accession, and spherical to oblate-shaped. The pulp represented between 50 and 70% of the weight of the whole fruit. The pulp adhered only partially to the seeds in 5 of the 6 accessions studied, while the last one exhibited full adherence. The fresh pulp was acidic, sweet, succulent and crunchy. The fruits studied had a variety of qualities, providing various opportunities for post-harvest uses: fruit salads, nectar preparation, jams and jellies, or export. We have established for the first time the total phenolic compounds and total flavonoids contents in the pulp of mamey apple fruits. The pulp colour was highly correlated with total phenolic compounds and total carotenoids contents.


Assuntos
Carotenoides/química , Flavonoides/química , Frutas/química , Mammea/química , Fenóis/química
10.
J Med Food ; 20(5): 485-490, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28504908

RESUMO

The methanol extract of Mammea longifolia Planch. and Triana (M. longifolia) fruit was studied for anticancer and apoptotic effects in the SW480 colon cancer cell line. The apoptotic and necrotic effects of M. longifolia were detected by 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) and lactate dehydrogenase assays, respectively. One hundred µg/mL of the extract killed ∼82.4% of the cells; however, 2% of the death was related to necrosis. The morphological changes in M. longifolia-stimulated SW480 cells were observed directly by light microscopy. DNA fragmentation assay was employed to analyze the apoptosis induction. M. longifolia-treated SW480 cells promoted the expression of Bax, Bad, cleaved-poly-ADP-ribose polymerase (PARP), and p53 proteins and decreased the protein expression of pro-caspases Bcl-2 and Bcl-XL. The ratios of Bax/Bcl-2 and cleaved-PARP/PARP, predictive markers of apoptotic stimuli in cancer, increased and may play an important role in regulating the progression of apoptosis. The results suggested that M. longifolia induces cell death via mitochondrial-related apoptosis in SW480 cells.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias do Colo/fisiopatologia , Mammea/química , Mitocôndrias/efeitos dos fármacos , Extratos Vegetais/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Frutas/química , Humanos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Supressora de Tumor p53/genética
11.
BMC Complement Altern Med ; 17(1): 57, 2017 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-28100218

RESUMO

BACKGROUND: The transmission of Dengue virus (DENV) and Chikungunya virus (CHIKV) has increased worldwide, due in part to the lack of a specific antiviral treatment. For this reason, the search for compounds with antiviral potential, either as licensed drugs or in natural products, is a research priority. The objective of this study was to identify some of the compounds that are present in Mammea americana (M. americana) and Tabernaemontana cymosa (T. cymosa) plants and, subsequently, to evaluate their cytotoxicity in VERO cells and their potential antiviral effects on DENV and CHIKV infections in those same cells. METHODS: Dry ethanolic extracts of M. americana and T. cymosa seeds were subjected to open column chromatographic fractionation, leading to the identification of four compounds: two coumarins, derived from M. americana; and lupeol acetate and voacangine derived from T. cymosa.. The cytotoxicity of each compound was subsequently assessed by the MTT method (at concentrations from 400 to 6.25 µg/mL). Pre- and post-treatment antiviral assays were performed at non-toxic concentrations; the resulting DENV inhibition was evaluated by Real-Time PCR, and the CHIKV inhibition was tested by the plating method. The results were analyzed by means of statistical analysis. RESULTS: The compounds showed low toxicity at concentrations ≤ 200 µg/mL. The compounds coumarin A and coumarin B, which are derived from the M. americana plant, significantly inhibited infection with both viruses during the implementation of the two experimental strategies employed here (post-treatment with inhibition percentages greater than 50%, p < 0.01; and pre-treatment with percentages of inhibition greater than 40%, p < 0.01). However, the lupeol acetate and voacangine compounds, which were derived from the T. cymosa plant, only significantly inhibited the DENV infection during the post-treatment strategy (at inhibition percentages greater than 70%, p < 0.01). CONCLUSION: In vitro, the coumarins are capable of inhibiting infection by DENV and CHIKV (with inhibition percentages above 50% in different experimental strategies), which could indicate that these two compounds are potential antivirals for treating Dengue and Chikungunya fever. Additionally, lupeol acetate and voacangine efficiently inhibit infection with DENV, also turning them into promising antivirals for Dengue fever.


Assuntos
Antivirais/uso terapêutico , Febre de Chikungunya/tratamento farmacológico , Dengue/tratamento farmacológico , Mammea/química , Extratos Vegetais/uso terapêutico , Tabernaemontana/química , Animais , Chlorocebus aethiops , Citotoxinas/toxicidade , Mammea/toxicidade , Extratos Vegetais/toxicidade , Tabernaemontana/toxicidade , Células Vero , Replicação Viral/efeitos dos fármacos
12.
Chem Pharm Bull (Tokyo) ; 64(7): 880-5, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27373643

RESUMO

A methanol extract of the flowers of Mammea siamensis (Calophyllaceae) was found to inhibit enzymatic activity against aromatase (IC50=16.5 µg/mL). From the extract, two new geranylated coumarins, mammeasins C (1) and D (2), were isolated together with seven coumarins: 8-hydroxy-5-methyl-7-(3,7-dimethyl-octa-2,6-dienyl)-9-(2-methyl-1-oxobutyl)-4,5-dihydropyrano[4,3,2-de]chromen-2-one (9), 8-hydroxy-5-methyl-7-(3,7-dimethyl-octa-2,6-dienyl)-9-(3-methyl-1-oxobutyl)-4,5-dihydropyrano[4,3,2-de]chromen-2-one (10), mammeas A/AA (14), A/AB (15), A/AA cyclo D (18), E/BA (23), and E/BC cyclo D (25). The structures of 1 and 2 were elucidated on the basis of spectroscopic evidence. Among the isolates including 17 previously reported coumarins, 1 (IC50=2.7 µM), 2 (3.6 µM), and mammea B/AB cyclo D (21, 3.1 µM) showed relatively strong inhibitory activities comparable to the activity of the synthetic nonsteroidal aromatase inhibitor aminoglutethimide (2.0 µM).


Assuntos
Inibidores da Aromatase/farmacologia , Aromatase/metabolismo , Cumarínicos/farmacologia , Flores/química , Mammea/química , Inibidores da Aromatase/química , Inibidores da Aromatase/isolamento & purificação , Cumarínicos/química , Cumarínicos/isolamento & purificação , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Proteínas Recombinantes/metabolismo , Relação Estrutura-Atividade
13.
BMC Complement Altern Med ; 16: 130, 2016 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-27193767

RESUMO

BACKGROUND: Wilms' tumor 1 (WT1) is a biological marker for predicting leukemia progression. In this study, mammea E/BB, an active compound from Saraphi (Mammea siamensis) seed extract was examined for its effect on down-regulatory mechanism of WT1 gene expression, WT1 protein and mRNA stability, and cell proliferation in K562 cell line. METHODS: M. siamensis seeds were obtained from the region of Chiang Mai (North of Thailand). Mammea E/BB was extracted from seeds of M. siamensis. WT1 protein expression and stability were evaluated by Western blot analysis. WT1 mRNA stability was assessed by qRT-PCR. WT1-DNA binding and WT1 promoter activity were assayed by ChIP assay and luciferase-reporter assay, respectively. Cell cycle arrest was studied by flow cytometry. RESULTS: Treatment with mammea E/BB led to down-regulation of WT1 expression. The suppression of WT1 expression did not involve protein and mRNA degradation. Rather, WT1 protein was down-regulated through disruption of transcriptional auto-regulation of the WT1 gene. Mammea E/BB inhibited WT1-DNA binding at the WT1 promoter and decreased luciferase activity. It also disrupted c-Fos/AP-1 binding to the WT1 promoter via ERK1/2 signaling pathway and induced S phase cell cycle arrest in K562 cells. CONCLUSION: Mammea E/BB had pleotropic effects on kinase signaling pathways, resulting in inhibition of leukemia cell proliferation.


Assuntos
Cumarínicos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Mammea/química , Extratos Vegetais/farmacologia , Proteínas WT1/biossíntese , Proliferação de Células/efeitos dos fármacos , Cumarínicos/química , Humanos , Células K562 , Estrutura Molecular , Estabilidade de RNA/efeitos dos fármacos , RNA Neoplásico , Proteínas WT1/genética
14.
Nat Prod Res ; 30(4): 443-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25738951

RESUMO

Mammea siamensis is used in traditional Thai medicine. This study was designed to extract and isolate an active compound from the M. siamensis seeds and to investigate its activity on Wilms' tumour 1 (WT1) protein expression in K562 cells. WT1 is a transcription factor that stimulates cell proliferation. The ethanol saraphi seed (ESS) extract was fractionated using n-hexane, ethyl acetate, n-butanol and water to obtain n-hexane saraphi seed (HSS), ethyl acetate saraphi seed (EASS), n-butanol saraphi seed (BSS), and water saraphi seed (WSS) extracts, respectively. The ESS, HSS and EASS extracts had strong cytotoxic effects on K562 cells in the MTT assay. All three fractions decreased WT1 protein levels and decreased total cell numbers. The HSS extract decreased the WT1 protein levels in a time- and dose-dependent manner. HPLC and NMR analyses indicated that the active compound of HSS was mammea E/BB. M. siamensis seeds are thus identified as a promising source of bioactive compounds for potential inhibition of WT1 protein expression.


Assuntos
Cumarínicos/farmacologia , Mammea/química , Extratos Vegetais/farmacologia , Proteínas WT1/metabolismo , Cromatografia Líquida de Alta Pressão , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Células K562/efeitos dos fármacos , Estrutura Molecular , Sementes/química
15.
Molecules ; 20(10): 17735-46, 2015 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-26404214

RESUMO

Through dereplication analysis, seven known Mammea coumarins were identified in a fraction obtained from Mammea neurophylla dichloromethane bark extract selected for its ability to prevent advanced glycation end-product (AGE) formation. Among them, a careful examination of the NMR dataset of pedilanthocoumarin B led to a structural revision. Inspection of LC-DAD-MS(n) chromatograms allowed us to predict the presence of four new compounds, which were further isolated. Using spectroscopic methods (¹H-, (13)C- and 2D-NMR, HRMS, UV), these compounds were identified as new benzoyl substituted 4-phenylcoumarins (iso-pedilanthocoumarin B and neurophyllol C) and 4-(1-acetoxypropyl)coumarins cyclo F (ochrocarpins H and I).


Assuntos
Cumarínicos/química , Mammea/química , Casca de Planta/química , Extratos Vegetais/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular
16.
J Med Assoc Thai ; 97 Suppl 8: S149-55, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25518307

RESUMO

BACKGROUND: Sa-Tri-Lhung-Klod is a Thai traditional medicine remedy for postpartum in the lists of The National Drug List ofHerbal Medicine Products AD. It consists ofseventeen herbs and were obtained by maceration and used in the form of liquor for women's health care such as treatment ofamenorrhea, menopause and blood tonic. In addition, it also usedfor postpartum care for being anti-inflammation in postpartum and prevention of cancer in women. OBJECTIVE: To investigate cytotoxic activity ofSa-Tri-Lhung-Klod remedy extracts and its herbal ingredients against human ovarian carcinoma cell line (SKOV-3) and cervical adenocarcinoma (HeLa) cell line. MATERIAL AND METHOD: Sa-Tri-Lhung-Klod remedy and its plant ingredients were extracted by maceration in 95% ethanol and dried using evaporator. All extracts were testedfor cytotoxic activity by sulforhodamine B (SRB) assay. RESULTS: Ethanolic extract ofSa-Tri-Lhung-Klod remedy displayed cytotoxic activity against SKOV-3 and HeLa with IC50 values of 72.84±1.07 and 47.24±2.83 µg/ml, respectively. It was classified as "less-active" according to the NCI guideline. However, Caesalpinia sappan, Mammea siamensis and Curcuma comosa showed high cytotoxic activity against SKOV-3 with IC50 values of 9.55±1.38 13.45±0.82 and 14.21±1.30 µg/ml, respectively. The ethanolic extracts ofCaesalpiniasappan and Mammea siamensis also exhibited cytotoxic activity against HeLa with IC50 values of 6.30±0.06 and 7.72±0.11 µg/ml, respectively. CONCLUSION: These results support the use of Sa-Tri-Lhung-Klod remedy in Thai traditional medicine for preventing of ovarian cancer and cervical cancer Caesalpinia sappan, Curcuma comosa and Mammea siamensis were strikingly active against ovarian and cervical cancer cells. Their extracts have the potential for developing as new anti-cancer drugs for women health.


Assuntos
Adenocarcinoma , Neoplasias Ovarianas , Extratos Vegetais/farmacologia , Neoplasias do Colo do Útero , Caesalpinia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Curcuma , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células HeLa , Humanos , Técnicas In Vitro , Mammea , Medicina Tradicional , Plantas Medicinais
17.
Fitoterapia ; 96: 65-75, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24731922

RESUMO

Advanced glycation end-products (AGEs) are associated with many pathogenic disorders such as pathogenesis of diabetes or endothelial dysfunction leading to cardiovascular events. Therefore, the identification of new anti-AGE molecules or extracts aims at preventing such pathologies. Many Clusiaceae and Calophyllaceae species are used in traditional medicines to treat arterial hypertension as well as diabetes. Focusing on these plant families, an anti-AGE plant screening allowed us to select Mammea neurophylla for further phytochemical and biological studies. Indeed, both DCM and MeOH stem bark extracts demonstrated in vitro their ability to prevent inflammation in endothelial cells and to reduce vasoconstriction. A bioguided fractionation of these extracts allowed us to point out 4-phenyl- and 4-(1-acetoxypropyl)coumarins and procyanidins as potent inhibitors of AGE formation, potentially preventing endothelial dysfunction. The fractionation steps also led to the isolation of two new compounds, namely neurophyllols A and B from the DCM bark extract together with thirteen known mammea A and E coumarins (mammea A/AA, mammea A/AB, mammea A/BA, mammea A/BB, mammea A/AA cycloD, mammea A/AB cycloD, disparinol B, mammea A/AB cycloE, ochrocarpin A, mammea A/AA cycloF, mammea A/AB cycloF, mammea E/BA, mammea E/BB) as well as δ-tocotrienol, xanthones (1-hydroxy-7-methoxyxanthone, 2-hydroxyxanthone) and triterpenes (friedelin and betulinic acid). During this study, R,S-asperphenamate, previously described from fungal origin was also purified.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Biflavonoides/farmacologia , Catequina/farmacologia , Cumarínicos/farmacologia , Produtos Finais de Glicação Avançada/efeitos dos fármacos , Mammea/química , Extratos Vegetais/farmacologia , Proantocianidinas/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Biflavonoides/química , Biflavonoides/isolamento & purificação , Catequina/química , Catequina/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Cumarínicos/química , Cumarínicos/isolamento & purificação , Células Endoteliais , Frutas/química , Masculino , Estrutura Molecular , Triterpenos Pentacíclicos , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Proantocianidinas/química , Proantocianidinas/isolamento & purificação , Ratos , Ratos Wistar , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Xantonas/química , Xantonas/isolamento & purificação , Xantonas/farmacologia
18.
J Ethnopharmacol ; 147(1): 259-62, 2013 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-23466248

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The stem bark of Mammea africana is widely distributed in tropical Africa and commonly used in traditional medicine. This study aims to identify the active compound in Mammea africana and to evaluate its antimicrobial and antiproliferative activity. MATERIALS AND METHODS: Methanol extract from the bark of the Mammea africana was separated by liquid-liquid extraction, followed by open column chromatography. A principal antimicrobial compound was purified by high performance liquid chromatography (HPLC) and its structure was elucidated by nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). The antibacterial activity of the purified compound was determined using the broth microdilution method against 7 common pathogenic bacteria. The compound was also evaluated for cytotoxicity by cell proliferation assay (MTS) using the mouse embryonic fibroblast cell line NIH 3T3 and the non-small cell lung cancer cell line A549. RESULTS: The purified active compound was determined to be mammea A/AA and was found to be highly active against Campylobacter jejuni (MIC=0.5 µg/ml), Streptococcus pneumoniae (MIC=0.25 µg/ml), and Clostridium difficile (MIC=0.25 µg/ml). The compound exhibited significant antiproliferative activities against both NIH 3T3 and A549 cell lines. CONCLUSION: Mammea A/AA isolated from Mammea africana exerts specific inhibitory activity against Campylobacter jejuni, Streptococcus pneumoniae, and Campylobacter difficile. Mammea A/AA was also found to exhibit significant cytotoxicity against both cancer and normal cell lines.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Bactérias/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cumarínicos/farmacologia , Mammea , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/toxicidade , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Bactérias/crescimento & desenvolvimento , Campylobacter jejuni/efeitos dos fármacos , Campylobacter jejuni/crescimento & desenvolvimento , Linhagem Celular Tumoral , Fracionamento Químico , Cromatografia Líquida de Alta Pressão , Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/crescimento & desenvolvimento , Cumarínicos/química , Cumarínicos/isolamento & purificação , Cumarínicos/toxicidade , Relação Dose-Resposta a Droga , Humanos , Espectroscopia de Ressonância Magnética , Mammea/química , Espectrometria de Massas , Medicina Tradicional Africana , Metanol/química , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Células NIH 3T3 , Fitoterapia , Casca de Planta , Caules de Planta , Plantas Medicinais , Solventes/química , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/crescimento & desenvolvimento
19.
Bioorg Med Chem Lett ; 23(1): 158-62, 2013 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-23206866

RESUMO

On the search for anti-cancer compounds from Thai traditional herb medicines, a bioassay-guided fractionation and chemical investigation of the methanol extract of Mammea siamensis flower resulted in the isolation and identification of eight compounds (1-8) including a novel geranylated coumarin, namely mammeanoyl (2), and seven known compounds (1 and 3-8). The structure of new compound 2 was elucidated based on the extensive spectroscopic and chemical methods. Among the isolated compounds, three structurally related coumarins 3, 4, and 5 showed significant antiproliferative activities against human leukemia and stomach cancer cell lines. However, these compounds did not affect the cell viabilities of colon cancer, hepatoma, and normal skin fibroblast cell lines. Further analysis demonstrated that the morphological features of apoptosis including DNA fragmentation and chromatin condensation were observed in human leukemia HL-60 cells treated with compounds 3, 4, and 5. In addition, compound 3 led to caspase-3 activation and cleavage of poly (ADP-ribose) polymerase (PARP), and compound 3-induced DNA fragmentation was inhibited by caspase-specific inhibitors. These results suggest that compound 3, 4, and 5 exert antiproliferative actions through apoptotic cell death in leukemia cells and these compounds may have the potential to be developed into new anti-cancer drug candidates.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cumarínicos/química , Mammea/química , Antineoplásicos/síntese química , Antineoplásicos/química , Caspase 3/metabolismo , Linhagem Celular Tumoral , Cumarínicos/isolamento & purificação , Cumarínicos/farmacologia , DNA/metabolismo , Fragmentação do DNA , Ensaios de Seleção de Medicamentos Antitumorais , Flores/química , Células HL-60 , Humanos , Espectroscopia de Ressonância Magnética , Conformação Molecular , Poli(ADP-Ribose) Polimerases/metabolismo
20.
Rev. cuba. plantas med ; 17(4)oct.-dic. 2012.
Artigo em Espanhol | CUMED | ID: cum-53479

RESUMO

Introducción: el mamey amarillo (Mammea americana L.) se utiliza ampliamente en la curación de diversos tipos de enfermedades producidas por parásitos e insectos. Objetivo: realizar el tamizaje fitoquímico y determinar la actividad antibacteriana de los extractos secos de la tintura al 20 por ciento de las hojas y corteza del fuste de esta planta. Métodos: se recolectaron hojas y corteza del fuste de la planta objeto de estudio, que fueron lavadas, desinfectadas, secadas y pulverizadas. Luego se procedió a la elaboración de las tinturas al 20 por ciento por el método de maceración de la droga. Los extractos secos de las partes estudiadas de la planta se obtuvieron a partir de las tinturas al 20 por ciento y se emplearon para los ensayos del tamizaje fitoquímico y la evaluación de la actividad antibacteriana. Resultados: se comprobó la existencia de una alta diversidad de metabolitos secundarios, con predominio de los alcaloides, coumarinas, fenoles o taninos, quinonas y flavonoides. Los extractos secos mostraron actividad antibacteriana in vitro frente a la cepa de Staphylococcus aureus (ATCC 29737). Conclusiones: se destacan, por su significativa presencia, flavonoides, alcaloides, taninos y cumarinas, los cuales resultan de interés biológico y farmacológico por sus posibles aplicaciones terapéuticas(AU)


Introduction: the yellow mammee (Mammea americana L.) is widely used to cure different diseases caused by parasites and insects. Objective: to perform a phytochemical screening and to determine antibacterial activity of dry extracts of 20 percent tincture from the leaves and the bark of this plant. Methods: the leaves and stem bark of the plant were harvested, washed, disinfected, dried and crushed. Then it proceeded to the preparation of 20 percent tinctures through drug maceration. The dried extracts of the studied parts were obtained from the 20 percent tinctures and used to evaluate the phytochemical screening tests and the antibacterial activity. Results: the existence of a high diversity of secondary metabolites, predominantly alkaloids, coumarins, phenols and / or tannins, quinones, and flavonoids were confirmed. The dried extracts showed antibacterial activity in vitro against Staphylococcus aureus (ATCC 29737). Conclusions: flavonoids, alkaloids, tannins and coumarins, which are of biological and pharmacological interest for their potential therapeutic applications, were significantly present in these extracts(AU)


Assuntos
Extratos Vegetais , Mammea , Programas de Rastreamento , Antibacterianos
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