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1.
Molecules ; 27(14)2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-35889438

RESUMO

A study was conducted to investigate the anti-viral effect of a styrylpyrone derivative (SPD) called goniothalamin and the effects on the dengue virus serotype 2 (DENV-2) replication cycle. The SPD was prepared from the root of Goniothalamus umbrosus after purification with petroleum ether. The isolated SPD was then subjected to gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) analyses for structure validation. The cytotoxicity of the SPD was evaluated using a cell viability assay, while the anti-viral activity of the SPD towards DENV-2 was confirmed by conducting a foci reduction assay which involved virus yield reduction, time-of-addition, and time removal assays. Transcriptomic analysis via quantitative real-time polymerase chain reaction (qRT-PCR) using the DENV-2 E gene was conducted to investigate the level of gene transcript. Immunocytochemistry analysis was used to investigate the effects of SPD treatment on protein E expression. Finally, software molecular docking of the SPD and E protein was also performed. The cytotoxicity assay confirmed that the SPD was not toxic to Vero cells, even at the highest concentration tested. In the time-of-addition assay, more than 80% foci reduction was observed when SPDs were administered at 2 h post-infection (hpi), and the reduction percentage then dropped with the delay of the treatment time, suggesting the inhibition of the early replication cycle. However, the time removal assay showed that more than 80% reduction could only be observed after 96 h post-treatment with the SPD. Treatment with the SPD reduced the progeny infectivity when treated for 24 h and was dose-dependent. The result showed that transcript level of the E gene in infected cells treated with the SPD was reduced compared to infected cells without treatment. In immunocytochemistry analysis, the DENV-2 E protein exhibited similar expression trends, shown by the gene transcription level. Molecular docking showed that the SPD can interact with E protein through hydrogen bonds and other interactions. Overall, this study showed that SPDs have the potential to be anti-DENV-2 via a reduction in viral progeny infectivity and a reduction in the expression of the DENV-2 E gene and protein at different phases of viral replication. SPDs should be further researched to be developed into an effective anti-viral treatment, particularly for early-phase dengue viral infection.


Assuntos
Vírus da Dengue , Dengue , Goniothalamus , Animais , Antivirais/química , Chlorocebus aethiops , Dengue/tratamento farmacológico , Humanos , Simulação de Acoplamento Molecular , Sorogrupo , Células Vero , Replicação Viral
2.
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
3.
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
4.
Z Naturforsch C J Biosci ; 75(11-12): 485-488, 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-32966236

RESUMO

This study was aimed to investigate the chemical compositions of the essential oils from Goniothalamus macrophyllus and Goniothalamus malayanus growing in Malaysia. The essential oils were obtained by hydrodistillation and fully characterized by gas chromatography (GC-FID) and gas chromatography-mass spectrometry (GC-MS). Analyses of the essential oils from G. macrophyllus and G. malayanus resulted in 93.6 and 95.4% of the total oils, respectively. The major components of G. macrophyllus oil were germacrene D (25.1%), bicyclogermacrene (11.6%), α-copaene (6.9%) and δ-cadinene (6.4%), whereas in G. malayanus oil bicyclogermacrene (43.9%), germacrene D (21.1%) and ß-elemene (8.4%) were the most abundant components.


Assuntos
Goniothalamus/química , Óleos Voláteis/química , Folhas de Planta/química , Cicloexanonas/química , Cicloexanonas/isolamento & purificação , Cromatografia Gasosa-Espectrometria de Massas , Plantas Medicinais/química , Sesquiterpenos Policíclicos/química , Sesquiterpenos Policíclicos/isolamento & purificação , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/isolamento & purificação
5.
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
6.
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
7.
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
8.
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
9.
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
10.
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
11.
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
12.
Sci Rep ; 6: 35674, 2016 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-27767040

RESUMO

The floral phenology, pollination ecology and breeding systems of two sympatric early-divergent angiosperms, Goniothalamus tapisoides and G. suaveolens (Annonaceae) are compared. The flowers are protogynous and morphologically similar, with anthesis over 23-25 h. Both species are predominantly xenogamous and pollinated by small beetles: G. tapisoides mainly by Curculionidae and G. suaveolens mainly by Nitidulidae. Coevolution and reproductive resource partitioning, reducing interspecific pollen transfer, is achieved by temporal isolation, due to contrasting floral phenologies; and ethological isolation, due to contrasting floral scents that contain attractants specific to the two beetle families. Analysis of floral scents revealed three volatiles (3-methylbutyl acetate, ethyl hexanoate and 2-phenylethanol) that are known to be nitidulid attractants in the floral scent of G. suaveolens, but absent from that of G. tapisoides. An effective pollinator trapping mechanism is demonstrated for both species, representing the first such report for the family. Trapping is achieved by the compression of the outer petals against the apertures between the inner petals. This trapping mechanism is likely to be a key evolutionary innovation for Goniothalamus, increasing pollination efficiency by increasing pollen loading on beetles during the staminate phase, promoting effective interfloral pollinator movements, and increasing seed-set by enabling rapid turn-over of flowers.


Assuntos
Goniothalamus/fisiologia , Animais , Bornéu , Besouros/fisiologia , DNA de Plantas/genética , Ecossistema , Flores/anatomia & histologia , Flores/crescimento & desenvolvimento , Especiação Genética , Goniothalamus/anatomia & histologia , Goniothalamus/genética , Repetições de Microssatélites , Odorantes , Melhoramento Vegetal , Polinização/fisiologia , Reprodução/fisiologia , Simpatria/genética , Simpatria/fisiologia , Termogênese
13.
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 Genética/efeitos dos fármacos
14.
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
15.
Org Lett ; 18(5): 968-71, 2016 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-26890072

RESUMO

A photochemical approach to the cytotoxic lactone (+)-goniofufurone (1) is reported. Paternò-Büchi [2 + 2] photocycloaddition from known enol ether 4, derived from the readily available sugar d-isosorbide, yielded oxetane 7. This slow, dilute reaction was scaled up by using flow photochemistry to yield >40 g of 7. Installation of the key lactone ring was achieved via a unique Wacker-style oxidation of an enol-ether bond. Acid-catalyzed aqueous ring opening provided 1 in five steps from 4 (11.5% overall).


Assuntos
Citotoxinas/síntese química , Lactonas/síntese química , Lactonas/farmacologia , Catálise , Citotoxinas/química , Citotoxinas/farmacologia , Éteres Cíclicos , Goniothalamus/química , Lactonas/química , Estrutura Molecular , Fotoquímica , Estereoisomerismo
16.
Mol Phylogenet Evol ; 92: 124-39, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26134978

RESUMO

A phylogenetic study of the genus Goniothalamus (Annonaceae) is presented using maximum parsimony, maximum likelihood and Bayesian approaches, with 65 species sampled (48.5% of the genus) based on sequences of nine chloroplast DNA regions (11,214 aligned positions). The resultant phylogeny clearly indicates that Goniothalamus is monophyletic. Preliminary research initially focused on identifying synapomorphies and estimating the phylogenetic signal of selected morphological characters based on parsimony and likelihood ancestral character state reconstructions. This prescreening of characters enabled 40 to be selected for further study, and of these 15 are shown here to demonstrate significant phylogenetic signal and to provide clear synapomorphies for several infrageneric clades. Although floral structure in Goniothalamus is comparatively uniform, suggesting a common basic pattern of pollination ecology, fruit and seed morphology in the genus is very diverse and is presumably associated with different patterns of frugivory. The present study assesses correlations amongst fruit and seed characters which are putatively of functional importance with regard to frugivory and dispersal. One-way phylogenetic ANOVA indicates significant phylogenetically independent correlation between the following fruit and seed characters: fruits borne on older branches and/or on the main trunk have larger monocarps than fruits borne on young branches; and monocarps that contain seeds with a hairy testa are larger than those with glabrous seeds. We discuss fruit morphologies and potential explanations for the inferred correlations, and suggest that they may be the result of adaptation to different frugivores (birds, larger non-volant animal and primate seed dispersers, respectively).


Assuntos
Evolução Biológica , DNA de Cloroplastos/genética , Frutas/anatomia & histologia , Goniothalamus/genética , Filogenia , Sementes/anatomia & histologia , Análise de Variância , Sequência de Bases , Teorema de Bayes , Frutas/genética
17.
Nat Prod Commun ; 10(5): 725-7, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26058144

RESUMO

Goniothalamin produced by the Malaysian medicinal plant, Goniothalamus andersonii J. Sinclair, strongly inhibits plant growth. However, its mode of action has not been characterized at the gene expression level. We conducted DNA microarray assay to analyze the changes in early gene responses of Arabidopsis thaliana seedlings. After a 6-h exposure to goniothalamin, we observed an upregulation of genes highly associated with heat response, and 22 heat shock protein (AtHSP) genes were upregulated more than 50 fold. Together with these genes, we observed upregulation of the genes related to oxidative stress and protein folding. Also, the genes related to cell wall modification and cell growth, expansin (AtEXPA) genes, were significantly downregulated. The results suggested that goniothalamin induces oxidative stresses and inhibits the expression of cell wall-associated proteins resulting in growth inhibition of Arabidopsis seedlings.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/efeitos dos fármacos , Arabidopsis/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Goniothalamus/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Pironas/farmacologia , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Perfilação da Expressão Gênica , Malásia , Análise de Sequência com Séries de Oligonucleotídeos , Plântula/efeitos dos fármacos , Plântula/genética , Plântula/crescimento & desenvolvimento , Plântula/metabolismo
18.
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
19.
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
20.
Trop Biomed ; 31(1): 89-96, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24862048

RESUMO

Trypanosoma evansi, the causative agent of "surra", infects many species of wild and domestic animals worldwide. In the current study, the aqueous and ethanolic extracts of six medicinal plants, namely, Aquilaria malaccensis, Derris elliptica, Garcinia hombroniana, Goniothalamus umbrosus, Nigella sativa, and Strobilanthes crispus were screened in vitro for activity against T. evansi. The cytotoxic activity of the extracts was evaluated on green monkey kidney (Vero) cells using MTT-cell proliferation assay. The median inhibitory concentrations (IC50) of the extracts ranged between 2.30 and 800.97 µg/ml and the median cytotoxic concentrations (CC50) ranged between 29.10 µg/ml and 14.53 mg/ml. The aqueous extract of G. hombroniana exhibited the highest selectivity index (SI) value of 616.36, followed by A. malaccensis aqueous extract (47.38). Phytochemical screening of the G. hombroniana aqueous extract revealed the presence of flavonoids, phenols, tannins, and saponins. It is demonstrated here that the aqueous extract of G. hombroniana has potential antitrypanosomal activity with a high SI, and may be considered as a potential source for the development of new antitrypanosomal compounds.


Assuntos
Flavonoides/farmacologia , Magnoliopsida/química , Extratos Vegetais/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma/efeitos dos fármacos , Tripanossomíase/tratamento farmacológico , Acanthaceae/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Derris/química , Flavonoides/química , Flavonoides/isolamento & purificação , Garcinia/química , Goniothalamus/química , Concentração Inibidora 50 , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Plantas Medicinais , Sementes/química , Thymelaeaceae/química , Tripanossomicidas/química , Tripanossomicidas/isolamento & purificação , Tripanossomíase/parasitologia , Células Vero
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