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1.
Sci Rep ; 14(1): 7962, 2024 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575628

RESUMO

The underlying study was carried out aiming at transdermal drug delivery (TDD) of Goniothalamus macrophyllus as sono-photo-sensitizer (SPS) using microneedle (MN) arrays with iontophoresis (MN-IP), electroporation (MN-EP) in conjunction with applying photodynamic therapy (PDT), sonodynamic therapy (SDT) and sono-photodynamic therapy (SPDT) as an up-to-date activated cancer treatment modality. Study was conducted on 120 male Swiss Albino mice, inoculated with Ehrlich ascites carcinoma (EAC) divided into 9 groups. We employed three different arrays of MN electrodes were used (parallel, triangular, and circular), EP, IP with different volts (6, 9, 12 V), an infrared laser and an ultrasound (pulsed and continuous wave) as our two energy sources. Results revealed that parallel 6 V TDD@MN@IP@EP can be used as effective delivery system for G. macrophyllus from skin directly to target EAC cells. In addition MN@IP@EP@TDD G. macrophyllus is a potential SPS for SPDT treatment of EAC. With respect to normal control mice and as opposed to the EAC untreated control mice, MN@EP@IP TDD G. macrophyllus in the laser, ultrasound, and combination activated groups showed a significant increase in the antioxidant markers TAC level and the GST, GR, Catalase, and SOD activities, while decrease in lipid peroxidation oxidative stress parameter MDA levels. In addition significantly increased apoptotic genes expressions (p53, caspase (3, 9), Bax, and TNF alpha) and on the other hand decreased anti- apoptotic (Bcl-2) and angiogenic (VEGF) genes expressions. Moreover significantly ameliorate liver and kidney function decreasing ALT, AST, urea and creatinine respectively. Furthermore MN@IP@EP@TDD G. macrophyllus combined with SPDT was very effective at reducing the growth of tumors and even causing cell death according to microscopic H&E stain results. This process may be related to a sono- and/or photochemical activation mechanism. According to the findings, MN@IP@EP@TDD G. macrophyllus has a lot of potential as a novel, efficient delivery method that in combination with infrared laser and ultrasound activation SPDT demonstrated promising anticancer impact for treating cancer.


Assuntos
Carcinoma , Goniothalamus , Masculino , Animais , Camundongos , Iontoforese , Administração Cutânea , Pele/metabolismo , Eletroporação/métodos , Carcinoma/metabolismo
2.
J Nat Prod ; 87(4): 1023-1035, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38536967

RESUMO

The plant Goniothalamus leiocarpus of the Annonaceae family is used as an alternative medicine in tropical regions. Applying high-speed counter current chromatography (HSCCC), eight new bioactive styrylpyrone isomers, including 6R,7S,8R,2'S-goniolactone B (1), 6S,7S,8S,2'S-goniolactone B (2), 6R,7R,8R,2'S-goniolactone B (3), 6R,7S,8S,2'S-goniolactone C (4), 6R,7S,8R,2'S-goniolactone C (5), 6S,7R,8S,2'S-goniolactone C (6), and two positional isomers, 6R,7R,8R,2'S-goniolactone G (7) and 6S,7R,8R,2'S-goniolactone G (8), were isolated from a chloroform fraction (2.1 g) of G. leiocarpus, which had a prominent spot by TLC analysis. The structures of the new compounds were elucidated by MS, NMR, IR, and UV spectra, and their absolute configurations were determined by Mosher's method, ECD, and X-ray diffraction analysis. The isolates are characteristic components found in plants of the genus Goniothalamus and consist of two structural moieties: a styrylpyrone and a dihydroflavone unit. The isolation of the eight new compounds demonstrates the effectiveness of HSCCC in separating the isomers of natural styrylpyrone. In a bioactivity assessment, compounds 1 and 6 exhibited cytotoxic effects against the human colon carcinoma cell lines LS513 and SW620 with IC50 values ranging from 1.6 to 3.9 µM. Compounds 1, 2, 7, and 8 showed significant synergistic activity against antibiotic-resistant Staphylococcus aureus strains.


Assuntos
Goniothalamus , Casca de Planta , Pironas , Goniothalamus/química , Pironas/química , Pironas/farmacologia , Pironas/isolamento & purificação , Estrutura Molecular , Estereoisomerismo , Casca de Planta/química , Humanos , Distribuição Contracorrente/métodos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação
3.
Chem Biodivers ; 20(9): e202300371, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37477112

RESUMO

The phytochemical analysis of ethyl acetate and methanol extract of Goniothalamus wynaadensis Bedd. leaves led to an isolation of eight (1-8) known molecules, among them seven (2-8) isolated for the first time from this species, which includes (+)-goniothalamin oxide (2), goniodiol-7-monoacetate (3), goniodiol-8-monoacetate (4), goniodiol (5), (+)-8-epi-9-deoxygoniopypyrone (6) etc. The phytochemical modification by acetylation of 3 and 4 gave goniodiol diacetate (9) with absolute configuration (6R, 7R, 8R) confirmed by single crystal X-ray diffraction. Compounds 3-9 were cytotoxic against breast, ovarian, prostate and colon cancer cell lines with IC50 <10 µM. Cell cycle analysis and Annexin-V assay on MDA-MB-231 cell using goniodiol-7-monoacetate (3) exhibited apoptotic response as well as necrotic response and showed cell proliferation arrest at G2/M phase. An in silico target identification for these molecules was carried out with an α-tubulin protein target by covalent docking. To gain an in-depth understanding and identify the stability of these protein-ligand complexes on thermodynamic energy levels, further assessment of the isolated molecules binding to the Cys-316 of α-tubulin was performed based on reaction energetic analysis via DFT studies which hinted the isolated molecules may be α-tubulin inhibitors similar to Pironetin. Molecular dynamics reiterated the observations.


Assuntos
Antineoplásicos , Goniothalamus , Estrutura Molecular , Tubulina (Proteína)/metabolismo , Estirenos/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Proliferação de Células , Simulação de Acoplamento Molecular , Ensaios de Seleção de Medicamentos Antitumorais , Linhagem Celular Tumoral , Apoptose , Relação Estrutura-Atividade
4.
Molecules ; 27(20)2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36296552

RESUMO

The tracing of an alternative drug, Phytochemicals is a promising approach to the viral threats that have emerged over the past two years. Across the world, herbal medicine is a better solution against anti-viral diseases during pandemic periods. Goniothalamus wightii is an herbal plant, which has diverse bioactive compounds with anticancer, antioxidant, and anti-viral properties. The aim of the study was to isolate the compound by chromatography studies and functionalization by FT-IR, LC-MS, and NMR (C-NMR, H-NMR). As a result, the current work focuses on whether (S)-Goniathalamin and its analogue could act as natural anti-viral molecules for multiple target proteins viz., MPro, RdRp, and SPro, which are required for SARS-CoV-2 infection. Overall, 954 compounds were examined and the molecular-docking studies were performed on the maestro platform of Schrodinger software. Molecular-dynamics simulation studies were performed on two complex major compounds to confirm their affinity across 150 simulations. This research suggests that plant-based drugs have high levels of antiviral properties against coronavirus. However, more research is needed to verify its antiviral properties.


Assuntos
Tratamento Farmacológico da COVID-19 , Goniothalamus , Humanos , SARS-CoV-2 , Proteases 3C de Coronavírus , Antioxidantes , Espectroscopia de Infravermelho com Transformada de Fourier , Cisteína Endopeptidases/química , Antivirais/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , RNA Polimerase Dependente de RNA
5.
Fitoterapia ; 155: 105034, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34536533

RESUMO

Three previously undescribed benzopyranyl sesquiterpenes gracilipins BD (1-3) and two flavonoids 5,4'-dihydroxy-6-(2-hydroxybenzyl)-3,7,3'-trimethoxyflavone (4), and 5,4'-dihydroxy-8-(2-hydroxybenzyl)-3,7-dimethoxyflavone (5) were isolated from the leaves of Goniothalamus gracilipes (Annonaceae). Their structures were determined by analyses of MS and 2D NMR data. The absolute configurations of 1 were established by analysis of X-ray diffraction data. Cytotoxic evaluation of the compounds 1-5 against four cancer cell lines (KB, LU-1, HepG-2 and MCF-7) indicated that compound 5 had inhibitory activity against HepG-2 cell line with IC50 value of 16.7 µM. All new compounds (1-5) were evaluated for their antimicrobial activity against a panel of clinically significant microorganisms. Compound 2 showed significant antimicrobial effect on Staphylococus aureus with MIC value of 32 µg/mL.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Flavonoides/farmacologia , Goniothalamus/química , Sesquiterpenos/farmacologia , Antibacterianos/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Flavonoides/isolamento & purificação , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Folhas de Planta/química , Sesquiterpenos/isolamento & purificação , Staphylococcus aureus/efeitos dos fármacos , Vietnã
6.
Arch Pharm (Weinheim) ; 354(4): e2000446, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33522644

RESUMO

Cyclopolypeptides are among the most predominant biomolecules in nature, especially those derived from plant seeds. This category of compounds has gained extraordinary attention due to remarkable variety of structures and valuable biofunctions. These congeners display enormous variation in terms of both structure and function and are the most significant biomolecules due to their widespread bioproperties. The estrogenic activity, immunosuppressive activity, cytotoxicity, vasorelaxant activity, and other properties possessed by cyclic peptides from seeds of plants make these congeners attractive leads for the drug discovery process. The current study covers the important structural features, structure-activity relationship, synthesis methods, and bioproperties of plant seeds-originated bioactive peptides from Vaccaria segetalis, Linum usitatissimum, and Goniothalamus leiocarpus, which may prove vital for the development of novel therapeutics based on a peptide skeleton.


Assuntos
Produtos Biológicos/química , Peptídeos/química , Compostos Fitoquímicos/química , Plantas Medicinais/química , Sementes/química , Produtos Biológicos/metabolismo , Produtos Biológicos/farmacologia , Linho/química , Goniothalamus/química , Humanos , Conformação Molecular , Peptídeos/metabolismo , Peptídeos/farmacologia , Compostos Fitoquímicos/metabolismo , Compostos Fitoquímicos/farmacologia , Vaccaria/química
7.
J Ethnopharmacol ; 254: 112657, 2020 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-32045683

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria, a devastating infectious disease which was initially recognized as episodic fever, is caused by parasitic protozoan of the genus Plasmodium. Medicinal plants with ethnobotanical information to treat fever and/or malaria has been the key element in identifying potential plant candidates for antimalarial screening. Goniothalamus lanceolatus Miq. (Annonaceae) is used as a folk remedy, particularly to treat fever and skin diseases. AIM OF THE STUDY: In this context, supported with previous preliminary data of its antiplasmodial activity, this study was undertaken to determine the in vitro antiplasmodial and cytotoxicity activities of G. lanceolatus crude extracts and its major compounds. MATERIALS AND METHODS: The in vitro antiplasmodial activity was determined by parasite lactate dehydrogenase (pLDH) assay on chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum. The cytotoxicity activity was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on hepatocellular carcinoma (HepG2) and normal liver (WRL-68) cell lines. RESULTS: The root methanol extract possessed potent antiplasmodial activity against both P. falciparum 3D7 and K1 strains (IC50 = 2.7 µg/ml, SI = 140; IC50 = 1.7 µg/ml, SI = 236). Apart from the DCM extract of stem bark and root that were found to be inactive (IC50 > 50 µg/ml) against 3D7 strain, all other tested crude extracts exhibited promising (5< IC50 < 15 µg/ml) to moderate (15< IC50 < 50 µg/ml) antiplasmodial activity against both strain. Additionally, only compound C (Parvistone D) exerted promising antiplasmodial activity against 3D7 strain (IC50 = 7.5 µM, SI = 51) whereas compound A, B and D showed moderate antiplasmodial activity against the same strain (20 < IC50 < 100 µM). Interestingly, when tested on K1 strain, compound A, C and D exhibited promising antiplasmodial activity (2 < IC50 < 20 µM) while compound B exhibited moderate activity (IC50 = 26.9 µM). Cytotoxicity study showed that all tested crude extracts and compounds were non-toxic on WRL-68 and HepG2 cell lines (CC50 > 30 µg/ml, CC50 > 10 µM, respectively), except for the hexane and DCM extracts of root, which exerted mild cytotoxicity on HepG2 cell line (IC50 < 30 µg/ml). CONCLUSIONS: This study suggests that the root methanol extract and compound C (Parvistone D) obtained from G. lanceolatus are highly potential for exploitation as source of antimalarial agents. Parvistone D is identified as one of the bioactive styryl lactones found in the plant extract. It is also noteworthy, that the extract and compound were more active against chloroquine-resistant (K1) strain of P. falciparum. Further studies are being carried out to assess their toxicity profile and antimalarial efficacy in animal model.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Goniothalamus/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Linhagem Celular Tumoral , Células do Cúmulo , Relação Dose-Resposta a Droga , Etnofarmacologia , Humanos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Casca de Planta/química , Extratos Vegetais/química , Raízes de Plantas/química
8.
Phytochemistry ; 171: 112248, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31918304

RESUMO

The phytochemical investigation of the twig and leaf extracts of Goniothalamus tamirensis led to the isolation and identification of 15 compounds including three rare previously undescribed styryllactones, goniotamirenones A-C, together with 12 known compounds. (Z)-6-Styryl-5,6-dihydro-2-pyranone and 5-(1-hydroxy-3-phenyl-allyl)-dihydro-furan-2-one are reported here for the first time as previously undescribed natural products. Their structures were elucidated by spectroscopic methods. Goniotamirenone A was synthesized via a [2 + 2] cycloaddition reaction of 6-styrrylpyran-2-one in quantitative yield. The absolute configurations of goniotamirenones B and C were identified from experimental and calculated ECD data, while the absolute configurations of (-)-5-acetoxygoniothalamin, (-)-isoaltholactone, parvistone E, and 5-(1-hydroxy-3-phenyl-allyl)-dihydro-furan-2-one were identified by single-crystal X-ray diffraction analysis using Cu Kα radiation. The absolute configurations of the other related compounds were determined from comparisons of their ECD spectra with relevant compounds reported in the literature. (-)-5-Acetoxygoniothalamin exhibited potent cytotoxicity against the colon cancer cell line (HCT116) with an IC50 value of 8.6 µM which was better than the standard control (doxorubicin, IC50 = 9.7 µM), while (Z)-6-styryl-5,6-dihydro-2-pyranone was less active with an IC50 value of 22.1 µM.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Goniothalamus/química , Lactonas/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Estirenos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Teoria da Densidade Funcional , Ensaios de Seleção de Medicamentos Antitumorais , Células HCT116 , Humanos , Lactonas/química , Lactonas/isolamento & purificação , Modelos Moleculares , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Estirenos/química , Estirenos/isolamento & purificação
9.
J Nat Prod ; 82(9): 2430-2442, 2019 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-31433181

RESUMO

Eight new bis-styryllactones, goniolanceolatins A-H (1-8), possessing a rare α,ß-unsaturated δ-lactone moiety with a (6S)-configuration, were isolated from the CH2Cl2 extract of the stembark and roots of Goniothalamus lanceolatus Miq., a plant endemic to Malaysia. Absolute structures were established through extensive 1D- and 2D-NMR data analysis, in combination with electronic dichroism (ECD) data. All of the isolates were evaluated for their cytotoxicity against human lung and colorectal cancer cell lines. Compounds 2 and 4 showed cytotoxicity, with IC50 values ranging from 2.3 to 4.2 µM, and were inactive toward human noncancerous lung and colorectal cells. Compounds 1, 3, 6, 7, and 8 showed moderate to weak cytotoxicity. Docking studies of compounds 2 and 4 showed that they bind with EGFR tyrosine kinase and cyclin-dependent kinase 2 through hydrogen bonding interactions with the important amino acids, including Lys721, Met769, Asn818, Arg157, Ile10, and Glu12.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Goniothalamus/química , Lactonas/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Lactonas/química , Lactonas/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/farmacologia
10.
Phytochemistry ; 157: 8-20, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30352328

RESUMO

Eight previously undescribed compounds, including four alkaloids and five styryllactones together with 36 known compounds were isolated from the twig and leaf extracts of Goniothalamus cheliensis. Their structures were elucidated by extensive analysis of their spectroscopic data. The absolute configuration of (-)-(4S,5S,6R,7S,8S)-goniochelienlactone and (-)-(4S,5S,6R,7S,8S)-7-acetylgoniochelienlactone were established from single crystal X-ray analysis using Cu Kα radiation. The absolute configurations of the other related compounds were identified by comparisons of their ECD spectra with those of related known compounds. Most of the isolated compounds were evaluated for their cytotoxicities against human colorectal cancer cells (HCT-116). Griffithazanone A was the most potent with an IC50 value of 2.39 µM.


Assuntos
Alcaloides/química , Alcaloides/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Goniothalamus/química , Lactonas/química , Lactonas/farmacologia , Alcaloides/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Células HCT116 , Humanos , Lactonas/isolamento & purificação , Modelos Moleculares , Conformação Molecular
11.
Nat Prod Res ; 32(3): 287-293, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28714315

RESUMO

Two new linear acetogenins, gracilipin A (1) and methylsaccopetrin A (2) along with seven known compounds, saccopetrin A (3), 7,3',4'-trimethylquercetin (4), rhamnazin (5), casticin (6), isokanugin (7), melisimplexin (8) and 5-hydroxy-3,7-dimethoxy-3',4'-methylenedioxyflavone (9) were isolated from the fruits of Goniothalamus gracilipes Bân. Their structures were established by spectral analysis, such as mass spectrometry, 1D-NMR, 2D-NMR and circular dichroism (CD). Compounds 1 and 3 showed cytotoxic activity against KB cell line with IC50 values of 14.6 and 15.3 µM, respectively.


Assuntos
Acetogeninas/química , Antineoplásicos Fitogênicos/farmacologia , Goniothalamus/química , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Dicroísmo Circular , Frutas/química , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray
12.
Nat Prod Res ; 32(14): 1682-1689, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29098873

RESUMO

The ethanolic extract from the stem bark of Goniothalamus marcanii Craib was shown in preliminary brine shrimp lethality data having good cytotoxic activity. Further bioassay guided isolation was done by means of solvent partition, chromatography and precipitation to provide four isolated compounds: a novel compound 1 with the core structure of 1-azaanthraquinone moiety referred as marcanine G; as well as compounds 2-4 with known aristolactam structures namely, piperolactam C, cepharanone B and taliscanine. These compounds were characterised by spectroscopic techniques. The assessment of cytotoxicity was established on an SRB assay using doxorubicin as a positive control. Marcanine G (1) was considered the most active compound indicating the IC50 values of 14.87 and 15.18 µM against human lung cancer cells (A549) and human breast cancer cells (MCF7), respectively. However, 2 showed mild activity with the IC50 values of 83.72 and 82.32 µM against A549 and MCF7 cells, respectively.


Assuntos
Antraquinonas/química , Antraquinonas/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Goniothalamus/química , Ácidos Aristolóquicos/química , Ácidos Aristolóquicos/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração Inibidora 50 , Neoplasias Pulmonares/tratamento farmacológico , Estrutura Molecular , Casca de Planta/química , Extratos Vegetais/química
13.
Molecules ; 22(2)2017 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-28178219

RESUMO

Altholactone, a natural compound isolated from Goniothalamus spp., has demonstrated anti-inflammatory and anticancer activities, but its molecular mechanisms are still not fully defined. Nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) play pivotal roles in the cell survival of many human tumors. The objective of this study was to elucidate the mechanism of action of altholactone against prostate cancer DU145 cells and to evaluate whether its effects are mediated by inhibition of NF-κB and STAT3 activity. Altholactone inhibited proliferation of DU145 cells and induced cell cycle arrest in S phase and triggered apoptosis. Reporter assays revealed that altholactone repressed p65- and TNF-α-enhanced NF-κB transcriptional activity and also inhibited both constitutive and IL-6-induced transcriptional activity of STAT3. Consistent with this, altholactone down-regulated phosphorylation of STAT3 and moreover, decreased constitutively active mutant of STAT3 (STAT3C)-induced transcriptional activity. Altholactone treatment also results in down-regulation of STAT3 target genes such as survivin, and Bcl-2 followed by up regulation of pro-apoptotic Bax protein. However, pre-treatment with the antioxidant N-acetylcysteine (NAC) significantly inhibited the activation of Bax and prevented down-regulation of STAT3 target genes. Collectively, our findings suggest that altholactone induces DU145 cells death through inhibition of NF-κB and STAT3 activity.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Furanos/farmacologia , Pironas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Goniothalamus/química , Humanos , Masculino , NF-kappa B/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais
14.
Eur J Pharmacol ; 791: 455-464, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27640746

RESUMO

Styryl lactones are plant-derived compounds from genus Goniothalamus with promising anti-proliferation and anticancer properties. However, the exact mechanism and the target for their activities remained unclear. In the present study, we investigated the effect of 5-acetyl goniothalamin (5GTN) from Goniothalamus marcanii on Wnt/ß-catenin signaling pathway which is a key regulator in controlling cell proliferation in breast cancer cells (MCF-7 and MDA-MB-231). 5GTN, a naturally occurring derivative of goniothalamin (GTN) mediated the toxicity to MCF-7 and MDA-MB-231 cells in a dose- and time- related manner, and was more potent than that of GTN. 5GTN strongly inhibited cell proliferation and markedly suppressed transcriptional activity induced by ß-catenin in luciferase reporter gene assay. In consistent with this view, the expression of Wnt/ß-catenin signaling target genes including c-Myc, cyclin D1 and Axin2 in MCF-7 and MDA-MB-231 cells were suppressed after treatment with 5GTN. It was concomitant with cell cycle arrest at G1 phase and cell apoptosis in MCF-7 cells. In addition, 5GTN enhanced glycogen synthase kinase (GSK-3ß) activity and therefore reduced the expression of active form of ß-catenin protein in MCF-7 and MDA-MB-231 cells. Taken together, 5GTN exhibited a promising anticancer effect against breast cancer cells through an inhibition of Wnt/ß-catenin signaling. This pathway may be served as a potential chemotherapeutic target for breast cancer by 5GTN.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/patologia , Pironas/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Goniothalamus/química , Humanos , Lactonas/química , Lactonas/farmacologia , Fatores de Transcrição TCF/metabolismo , Transcrição Gênica/efeitos dos fármacos
15.
Asian Pac J Cancer Prev ; 17(7): 3281-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27509964

RESUMO

Bioactive compounds extracted from leaves and twigs of Goniothalamus griffithii include pinocembrin (PCN) and goniothalamin (GTN). The objectives of this study were to investigate the cytotoxic activities of PCN and GTN and their influence on molecular signaling for cell death in several human cancer cell lines compared to normal murine fibroblast NIH3T3 cells. GTN exhibited the most potent cytotoxicity against MCF7 > HeLa > HepG2 > NIH3T3 cells with IC50 values of 7.33, 14.8, 37.1 and 65.4 µM, respectively, whereas PCN was cytotoxic only to HepG2 cells with IC50 values of ~80 µM. Apoptotic cell death was confirmed by staining the cells with annexin VFITC and propidium iodide (PI) employing flow cytometry. Apoptosis was shown by externalization of phosphatidylserine in goniothalamintreated MCF7 cells in a dose response manner. Positive PIstained cells with the typical morphology of apoptotic cells were increased dosedependently. Furthermore, reduction of mitochondrial transmembrane potential was found in goniothalamintreated MCF7, HepG2 and HeLa cells. GTN treatment in MCF7 increased caspase3, 8 and 9 activities while GTNinduced HeLa cells showed an increase of both caspase3 and 9 activities. But an increased caspase8 activity was demonstrated in GTN and PCNtreated MCF7 and HepG2 cells, respectively. Taken together, GTN and PCNinduced human cancer cell apoptosis was through different molecular mechanisms or signaling pathways, which might be due to different machineries in different types of cancer cells, as evidenced by the compoundmodulated caspase activities in both intrinsic and/or extrinsic pathways.


Assuntos
Apoptose/efeitos dos fármacos , Goniothalamus/química , Neoplasias/tratamento farmacológico , Compostos Fitoquímicos/farmacologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Caspases/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Flavanonas/farmacologia , Células HeLa , Células Hep G2 , Humanos , Células MCF-7 , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Células NIH 3T3 , Neoplasias/metabolismo , Pironas/farmacologia , Transdução de Sinais/efeitos dos fármacos
16.
Fitoterapia ; 103: 206-12, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25865074

RESUMO

A new 2H-tetrahydropyran derivative, 6-epi-goniothalesdiol A (1), together with nine known styryllactones (2-10) and five known aristolactams (11-15) were isolated from the bark of Goniothalamus elegants Ast. The structures were elucidated by spectroscopic methods. The isolated compounds were evaluated for their cytotoxicity toward the KB, MCF7 and NCI-H187 cell lines as well as antimalarial and antimycobacterial activities. Compounds 4 and 10 showed strong activity against all three human cancer cell lines with IC50 values in the range of 0.538 to 4.25 µg/ml, while compounds 2, 4, 10 and 14 showed potent cytotoxicity against NCI-H187 with IC50 values in the range of 0.072 to 2.17 µg/ml. In addition, compounds 4, 6, 7, 9, 10 and 13 showed strong antiplasmodial activity with IC50 in the range of 2.28 to 5.89 µg/ml.


Assuntos
Antimaláricos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Furanos/farmacologia , Goniothalamus/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antimaláricos/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Furanos/isolamento & purificação , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Casca de Planta/química
17.
Biomed Res Int ; 2014: 536508, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25247178

RESUMO

The treatment of most cancers is still inadequate, despite tremendous steady progress in drug discovery and effective prevention. Nature is an attractive source of new therapeutics. Several medicinal plants and their biomarkers have been widely used for the treatment of cancer with less known scientific basis of their functioning. Although a wide array of plant derived active metabolites play a role in the prevention and treatment of cancer, more extensive scientific evaluation of their mechanisms is still required. Styryl-lactones are a group of secondary metabolites ubiquitous in the genus Goniothalamus that have demonstrated to possess antiproliferative activity against cancer cells. A large body of evidence suggests that this activity is associated with the induction of apoptosis in target cells. In an effort to promote further research on the genus Goniothalamus, this review offers a broad analysis of the current knowledge on Goniothalamin (GTN) or 5, 6, dihydro-6-styryl-2-pyronone (C13H12O2), a natural occurring styryl-lactone. Therefore, it includes (i) the source of GTN and other metabolites; (ii) isolation, purification, and (iii) the molecular mechanisms of actions of GTN, especially the anticancer properties, and summarizes the role of GTN which is crucial for drug design, development, and application in future for well-being of humans.


Assuntos
Goniothalamus/química , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Extratos Vegetais/uso terapêutico , Pironas/administração & dosagem , Animais , Antineoplásicos/administração & dosagem , Humanos , Resultado do Tratamento
18.
Nat Prod Commun ; 9(4): 495-8, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24868866

RESUMO

Two new styryllactones, macrocalactone (1) and 3-deoxycardiobutanolide (2), were isolated from the fruits of Goniothalamus macrocalyx Ban (Annonaceae), together with seven known compounds including four acetogenins, annonacin (3), solamin (4), isoannonacin (5), trans-murisolinone (6), and three other compounds, 7-acetylaltholactone (7), beta-caryophyllene-8R,9R-oxide (8) and 2-(2'-hydroxytetracosanoylamino)-octadecane-1,3,4-triol (9). Their structures were determined by spectroscopic and MS analysis. The absolute configuration of 1 was determined by X-ray crystallographic analysis. The structures of the acetogenins were confirmed by liquid chromatography coupled to a hybrid quadrupole-time of flight mass spectrometer, using post-column lithium infusion. The results were compared with the fragmentation obtained with a hybrid linear trap-orbitrap mass spectrometer. Compound 7 had cytotoxicity against KB, HepG2, Lu, and MCF7 cell lines with IC50 values of 13.1, 23.7, 26.3 and 60.2 microM, respectively, whereas annonacin (3) was selectively active against KB cells (IC50 value of 6.5 microM). The discovery of 3-deoxycardiobutanolide (2) from the fruits of this plant revealed that G. macrocalyx could be a valuable natural resource to obtain this compound as it has been previously reported to have a significant cytotoxicity against different cancer cell lines, especially HL-60 cells.


Assuntos
Acetogeninas/química , Frutas/química , Goniothalamus/química , Lactonas/química , Modelos Moleculares , Estrutura Molecular
19.
Nat Prod Commun ; 9(12): 1769-71, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25632481

RESUMO

A new acetogenin has been isolated from the ethyl acetate extract of leaves and twigs of G. sawtehii (Annonaceae). The structure of compound 1 was identified as sawtehtetronenin on the basis of spectral evidence (UV, IR, MS and 1H, and 13C NMR) and by comparison with related compounds. Sawtehtetronenin was found to be cytotoxic to human hepatocellular carcinoma HepG2 and breast cancer MDA-MB231 cells with IC50 values of 79.3 ± 11.9 µM and 108.1 ± 1.5 µM, respectively. Compound 1 was less toxic to both cell lines when compared with camptothecin, a chemotherapeutic drug.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Goniothalamus/química , Lactonas/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Células Hep G2 , Humanos , Lactonas/química , Lactonas/farmacologia , Folhas de Planta/química
20.
Food Chem Toxicol ; 59: 572-8, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23845509

RESUMO

(R)-(+)-Goniothalamin (GTN), a styryl-lactone isolated from the medicinal plant Goniothalamus macrophyllus, exhibits pharmacological activities including cytotoxic and anti-inflammatory effects. In this study, GTN modulated TNF-α induced NF-κB activation. GTN concentrations up to 20 µM showed low cytotoxic effects in K562 chronic myelogenous leukemia and in Jurkat T cells. Importantly, at these concentrations, no cytotoxicity was observed in healthy peripheral blood mononuclear cells. Our results confirmed that GTN inhibited tumor necrosis factor-α (TNF-α)-induced NF-κB activation in Jurkat and K562 leukemia cells at concentrations as low as 5 µM as shown by reporter gene assays and western blots. Moreover, GTN down-regulated translocation of the p50/p65 heterodimer to the nucleus, prevented binding of NF-κB to its DNA response element and reduced TNF-α-activated interleukin-8 (IL-8) expression. In conclusion, GTN inhibits TNF-α-induced NF-κB activation at non-apoptogenic concentrations in different leukemia cell models without presenting toxicity towards healthy blood cells underlining the anti-leukemic potential of this natural compound.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Descoberta de Drogas , Leucemia/tratamento farmacológico , NF-kappa B/metabolismo , Pironas/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/isolamento & purificação , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/isolamento & purificação , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Células Cultivadas , Genes Reporter/efeitos dos fármacos , Goniothalamus/química , Humanos , Interleucina-8/antagonistas & inibidores , Interleucina-8/metabolismo , Células Jurkat , Células K562 , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Malásia , NF-kappa B/agonistas , NF-kappa B/antagonistas & inibidores , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Raízes de Plantas/química , Transporte Proteico/efeitos dos fármacos , Pironas/efeitos adversos , Pironas/isolamento & purificação , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Elementos de Resposta/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
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