RESUMO
Liquid chromatography coupled with high-resolution mass spectrometry data-independent acquisition (LC-HRMS/DIA), including MSE, enable comprehensive metabolomics analyses though they pose challenges for data processing with automatic annotation and molecular networking (MN) implementation. This motivated the present proposal, in which we introduce DIA-IntOpenStream, a new integrated workflow combining open-source software to streamline MSE data handling. It provides 'in-house' custom database construction, allows the conversion of raw MSE data to a universal format (.mzML) and leverages open software (MZmine 3 and MS-DIAL) all advantages for confident annotation and effective MN data interpretation. This pipeline significantly enhances the accessibility, reliability and reproducibility of complex MSE/DIA studies, overcoming previous limitations of proprietary software and non-universal MS data formats that restricted integrative analysis. We demonstrate the utility of DIA-IntOpenStream with two independent datasets: dataset 1 consists of new data from 60 plant extracts from the Ocotea genus; dataset 2 is a publicly available actinobacterial extract spiked with authentic standard for detailed comparative analysis with existing methods. This user-friendly pipeline enables broader adoption of cutting-edge MS tools and provides value to the scientific community. Overall, it holds promise for speeding up metabolite discoveries toward a more collaborative and open environment for research.
Assuntos
Metabolômica , Software , Reprodutibilidade dos Testes , Fluxo de Trabalho , Metabolômica/métodos , Espectrometria de Massas/métodos , Cromatografia Líquida/métodosRESUMO
Schistosomiasis is a major neglected disease that imposes a substantial worldwide health burden, affecting approximately 250â million people globally. As praziquantel is the only available drug to treat schistosomiasis, there is a critical need to identify new anthelmintic compounds, particularly from natural sources. To enhance the activity of different natural products, one potential avenue involves its combination with silver nanoparticles (AgNP). Based on this approach, a one-step green method for the inâ situ preparation of dehydrodieugenol (DHDG) by oxidation coupling reaction using silver and natural eugenol is presented. AgNP formation was confirmed by UV-Vis spectroscopy due to the appearance of the surface plasmon resonance (SPR) band at 430â nm which is characteristic of silver nanoparticles. The nanoparticles were spherical with sizes in the range of 40 to 50â nm. Bioassays demonstrated that the silver nanoparticles loaded with DHDG exhibited significant anthelmintic activity against Schistosoma mansoni adult worms without toxicity to mammalian cells and an inâ vivo animal model (Caenorhabditis elegans), contributing to the development of new prototypes based on natural products for the treatment of schistosomiasis.
Assuntos
Anti-Helmínticos , Anti-Infecciosos , Produtos Biológicos , Eugenol/análogos & derivados , Lignanas , Nanopartículas Metálicas , Esquistossomose , Animais , Humanos , Prata/farmacologia , Prata/química , Nanopartículas Metálicas/química , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Esquistossomose/tratamento farmacológico , Anti-Infecciosos/uso terapêutico , Schistosoma mansoni , Produtos Biológicos/uso terapêutico , MamíferosRESUMO
Melanoma is a cancer type with high lethality, metastatic capacity, and limited therapeutic options. Different essential oils have been reported with antitumoral potential. Thus, the essential oil (EO) of the leaves of C. floribundus was obtained by hydrodistillation and analyzed by GC-MS. The majority of substances annotated were ß-selinene, E-Caryophyllene, and Premnaspirodiene. The cytotoxic activity of EO was evaluated on three melanoma cell lines SKMEL-147, WM-1366, and CHL-1, which are representative of metastatic melanoma with different mutation profiles. The IC50 values found for EO were lower than temozolomide (reference drug) in all melanoma cell lines. In addition, the selectivity of EO was upward when compared to the reference drug. Interestingly, the WM-1366â cell line was the most responsive, and these findings are very promising considering that it has shown high resistance to the plethora of compounds. Thus, the C. floribundus EO is a promising source to drive further studies for the development of new treatments for metastatic melanoma, which is urgently relevant given the resistance of this pathology to current treatments.
Assuntos
Antineoplásicos Fitogênicos , Proliferação de Células , Croton , Ensaios de Seleção de Medicamentos Antitumorais , Melanoma , Óleos Voláteis , Folhas de Planta , Humanos , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Folhas de Planta/química , Melanoma/tratamento farmacológico , Melanoma/patologia , Croton/química , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Relação Dose-Resposta a Droga , Sobrevivência Celular/efeitos dos fármacosRESUMO
Gibbilimbol B and analogues were isolated from the Brazilian plant Piper malacophyllum and displayed activity against trypomastigote forms of Trypanosoma cruzi as well as reduced toxicity against NCTC cells. These results stimulated the preparation of a series of 24 chemically related analogues to study the potential of these compounds against T. cruzi trypomastigotes and explore structure-activity relationships. Initially, 12 compounds were planned, maintaining the same extension of the linear side chain of gibbilimbol B and unsaturation on the C-4 position but changing the functional groups - ester and amide - and variating the substituent at the p-position in the aromatic ring. Other 12 compounds were prepared using a branched side chain containing an ethyl group at the C-2 position. Overall, these structurally-related analogues demonstrated promising activity against trypomastigote forms (EC50 < 20 µM) and no mammalian cytotoxicity to fibroblasts (CC50 > 200 µM). Using multivariate statistics and machine learning analysis, aspects associated with structure/activity were related to their three-dimensional structure and, mainly, to the substituents on the aromatic ring. Obtained results suggested that the presence of t-butyl or nitro groups at p-position with appropriate side chains causes an alteration in the electron topological state, Van der Waals volumes, surface areas, and polarizabilities of tested compounds which seem to be essential for biological activity against T. cruzi parasites.
Assuntos
Doença de Chagas , Tripanossomicidas , Trypanosoma cruzi , Humanos , Relação Estrutura-Atividade , Doença de Chagas/tratamento farmacológico , Análise Multivariada , Desenho de Fármacos , Tripanossomicidas/farmacologia , Tripanossomicidas/químicaRESUMO
One new aporphine, dicentrine-ß-N-oxide (1), together with five related known alkaloids dehydrodicentrine (2), predicentrine (3), N-methyllaurotetanine (4), cassythicine (5), and dicentrine (6) were isolated from the leaves of Ocotea puberula (Lauraceae). Antiprotozoal activity of the isolated compounds was evaluated inâ vitro against trypomastigote forms of Trypanosoma cruzi. Among the tested compounds, alkaloid 1 exhibited higher potential with EC50 value of 18.2â µM and reduced toxicity against NCTC cells (CC50 >200â µM - SI>11.0), similar to positive control benznidazole (EC50 of 17.7â µM and SI=10.7). Considering the promising results of dicentrine-ß-N-oxide (1) against trypomastigotes, the mechanism of parasite death caused by this alkaloid was investigated. As observed, this compound reached the plasma membrane electric potential directly after 2â h of incubation and triggered mitochondrial depolarization, which probably leads to trypomastigote death. Therefore, dicentrine-ß-N-oxide (1), reported for the first time in this work, can contribute to future works for the development of new trypanocidal agents.
Assuntos
Aporfinas/farmacologia , Membrana Celular/efeitos dos fármacos , Ocotea/química , Extratos Vegetais/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Aporfinas/química , Aporfinas/isolamento & purificação , Linhagem Celular , Membrana Celular/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Tripanossomicidas/química , Tripanossomicidas/isolamento & purificaçãoRESUMO
INTRODUCTION: Casearia is an essential source of cytotoxic highly oxidised clerodane diterpenes, in addition to phenolics, flavonoids, and glycoside derivatives. Here we identify flavonoid-3-O-glycoside derivatives in the ethyl acetate (EtOAc) fraction of the methanolic extract from leaves C. arborea leaves. OBJECTIVE: To characterise the EtOAc phase from the methanolic extract of C. arborea leaves using ultra-high-performance liquid chromatography diode array detector high-resolution tandem mass spectrometry (UHPLC-DAD-HRMS/MS) and molecular networking-based dereplication. Methodology We identified compounds not annotated in the GNPS platform by co-injection of standards in HPLC-DAD or by isolation and characterisation of the metabolites using nuclear magnetic resonance (NMR) spectroscopy. A workflow on the GNPS platform aided the organisation of spectral data and dereplication by annotations. We subjected the EtOAc phase to HPLC-DAD analysis using standard compound co-injection to corroborate the GNPS annotations. We isolated unidentified compounds with semi-preparative HPLC-DAD for structural identification using NMR. RESULTS: We annotated a molecular family of flavonoid-3-O-glycosides in the molecular networking created using the GNPS platform. These included avicularin, cacticin, isoquercitrin, quercitrin, rutin, and a quercetin-3-O-pentoside cluster. We confirmed the annotations with standard compounds using HPLC-DAD co-injection analysis, besides identifying quercetin-3-O-robinobioside and kaempferol. We isolated three flavonoid-3-O-pentosides and characterised them using one- and two-dimensional NMR; we identified them as reynoutrin, guaijaverin, and avicularin. CONCLUSION: This work describes the isolation of kaempferol and nine known flavonoid-3-O-glycosides from the polar fraction of the methanolic extract (EtOAc) from C. arborea leaves using molecular networking to guide the chromatographic procedures. We identified eight compounds for the first time in Casearia that amplify and reinforce the genus' chemotaxonomy with the presence of glycosylated flavonoids.
Assuntos
Casearia , Salicaceae , Cromatografia Líquida de Alta Pressão , Flavonoides/análise , Glicosídeos , Espectroscopia de Ressonância Magnética , Folhas de Planta/química , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
The genus Burkholderia is an emerging source of novel natural products chemistry, yet to date few methods exist for the selective isolation of strains of this genus from the environment. More broadly, tools to efficiently design selection media for any given genus would be of significant value to the natural products and microbiology communities. Using a modification of the recently published SMART protocol, we have developed a two-stage isolation protocol for strains from the genus Burkholderia. This method uses a combination of selective agar isolation media and multiplexed PCR profiling to derive Burkholderia strains from environmental samples with 95% efficiency. Creation of this new method paves the way for the systematic exploration of natural products chemistry from this important genus and offers new insight into potential methods for selective isolation method development for other priority genera.
Assuntos
Burkholderia/genética , Burkholderia/isolamento & purificação , Produtos Biológicos/química , Burkholderia/metabolismo , Biologia Computacional , Meios de Cultura/química , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Genoma Bacteriano , Filogenia , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/isolamento & purificação , Reprodutibilidade dos TestesRESUMO
Metabolomics approaches have become fundamental strategies for the analysis of complex mixtures, guiding the isolation of target compounds by focusing on unpublished or promising pharmacological properties. The discovery of novel anti-inflammatory agents is important due to several limitations regarding their potency, efficacy, and adverse effects. Thus, novel anti-inflammatory candidates are essential, aiming to find agents with better mechanisms of action. In this context, extracts from Poincianella pluviosa var. peltophoroides demonstrated significant in vivo anti-inflammatory potential. Thus, metabolomics analysis based on UHPLC-UV-HRFTMS data was performed for the identification of biomarkers with anti-inflammatory properties. Metabolomics-guided chromatographic process led to the isolation of novel compounds 4â´-methoxycaesalpinioflavone and 7-methoxycaesalpinioflavone, as well as known derivatives rhuschalcone VI and caesalpinioflavone. Isolated compounds caused edema inhibition and neutrophil recruitment. Two of them showed better efficacy than reference drugs (indomethacin and dexamethasone). Results of in vivo experiments corroborated those obtained through metabolomics and statistical analyses guiding the isolation of substances of interest.
Assuntos
Anti-Inflamatórios/farmacologia , Edema/tratamento farmacológico , Fabaceae/química , Metabolômica , Infiltração de Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/química , Edema/imunologia , Edema/patologia , Masculino , Camundongos , Neutrófilos/patologia , Extratos Vegetais/químicaRESUMO
A series of novel benzophenone derivatives containing a thiazole heterocyclic nucleus were designed by molecular hybridization. Molecular docking studies have demonstrated the inhibitory potential of the designed compounds against cyclooxygenase (COX) isoenzymes. These compounds were synthesized, characterized, and evaluated for their anti-inflammatory properties by the croton oil-induced ear edema assay to examine their effect on both prostaglandin (PG) production and neutrophils recruitment. The thiazole derivatives displayed a potent effect in terms of reducing ear edema. The analysis suggested that the presence of 4-phenyl-2-hydrazinothiazole and the absence of C4'-OCH3 on the benzophenone derivative structure are strongly related to the inhibition of PG production. In addition, the derivatives 2e, 3a and 3c concomitantly inhibit PG production and neutrophil recruitment, which may be a mechanism of action better than of common NSAIDs due to their inability to inhibit the neutrophil recruitment. Thus, these compounds can be considered as potential lead compounds toward the development of new anti-inflammatory drugs with an innovating mechanism of action.
Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Benzofenonas/química , Benzofenonas/farmacologia , Desenho de Fármacos , Edema/patologia , Infiltração de Neutrófilos/efeitos dos fármacos , Animais , Anti-Inflamatórios/síntese química , Benzofenonas/síntese química , Sítios de Ligação , Domínio Catalítico , Ciclo-Oxigenase 1/química , Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase/química , Modelos Animais de Doenças , Edema/tratamento farmacológico , Isomerismo , Camundongos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Ligação Proteica , Relação Estrutura-AtividadeRESUMO
Guarea macrophylla is a Brazilian plant species that has been used in folk medicine to treat a range of diseases. Our ongoing work focuses on the discovery of new bioactive natural products derived from Brazilian flora. The current study describes the identification of cytotoxic compounds from the EtOH extract of leaves from G. macrophylla using bioactivity-guided fractionation. This approach resulted in the isolation and characterization of four compounds: cycloart-23E-ene-3ß,25-diol (1), (23S*,24S*)-dihydroxycicloart-25-en-3-one (2), isopimara-7,15-diene-2α,3ß-diol (3), and isopimara-7,15-dien-3ß-ol (4), in which 2 and 3 are identified as new derivatives. In vitro assays were conducted to evaluate the cytotoxic activity of compounds 1-4 against a panel of cancer cell lines and to determine the possible mechanism(s) related to the activity of the compounds on B16F10Nex2 cells. The most active compound 1 induced cytotoxic effects on tumor cells, with IC50 values of 18.3, 52.1, and 58.9 µM against HL-60, HeLa, and B16F10-Nex2 tumor cells, respectively. Furthermore, it was observed in melanoma cells that compound 1 induced several specific apoptotic hallmarks, such as morphological changes in the cell shape structure, nuclear DNA condensation, specific chromatin fragmentation, and disruption in the mitochondrial membrane potential, which are related to the intrinsic apoptotic pathway.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Melanoma Experimental/tratamento farmacológico , Meliaceae/química , Extratos Vegetais/farmacologia , Terpenos/farmacologia , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Brasil , Linhagem Celular Tumoral , DNA de Neoplasias/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Células HL-60 , Células HeLa , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Estrutura Molecular , Folhas de Planta/química , Terpenos/química , Terpenos/isolamento & purificaçãoRESUMO
Bioactivity-guided fractionation of antileishmanial active extract from leaves of Casearia arborea led to isolation of three metabolites: tricin (1), 1',6'-di-O-ß-d-vanilloyl glucopyranoside (2) and vanillic acid (3). Compound 1 demonstrated the highest activity against the intracellular amastigotes of Leishmania infantum, with an IC50 value of 56 µm. Tricin (1) demonstrated selectivity in mammalian cells (SI > 7) and elicited immunomodulatory effect on host cells. The present work suggests that tricin modulated the respiratory burst of macrophages to a leishmanicidal state, contributing to the parasite elimination. Therefore, the natural compound tricin could be further explored in drug design studies for leishmaniasis treatment.
Assuntos
Antiprotozoários/isolamento & purificação , Casearia/química , Flavonoides/farmacologia , Animais , Antiprotozoários/farmacologia , Flavonoides/isolamento & purificação , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/farmacologia , Leishmania infantum/efeitos dos fármacos , Macrófagos Peritoneais/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Salicaceae , Ácido Vanílico/isolamento & purificação , Ácido Vanílico/farmacologiaRESUMO
The chemical composition and antimicrobial activity of essential oils obtained from three Brazilian plant species-leaves and branches of Eremanthus erythropappus (Asteraceae), leaves of Plectranthus barbatus, and leaves of P. amboinicus (Lamiaceae)-were determined. Analysis by GC/MS and determination of Kovats indexes both indicated δ-elemene (leaves-42.61% and branches-23.41%) as well as (-)-α-bisabolol (leaves-24.80% and stem bark-66.16%) as major constituents of E. erythropappus essential oils. The main components of leaves of P. barbatus were identified as (Z)-caryophyllene (17.98%), germacrene D (17.35%), and viridiflorol (14.13%); whereas those of leaves of P. amboinicus were characterized as p-cymene (12.01%), γ-terpinene (14.74%), carvacrol (37.70%), and (Z)-caryophyllene (14.07%). The antimicrobial activity against yeasts and bacteria was assessed in broth microdilution assays to determine the minimum inhibitory concentration (MIC) necessary to inhibit microbial growth. In addition, the crude oil of branches of E. erythropappus was subjected to chromatographic separation procedures to afford purified (-)-α-bisabolol. This compound displayed biological activity against pathogenic yeasts, thus suggesting that the antimicrobial effect observed with crude oils of E. erythropappus leaves and branches may be related to the occurrence of (-)-α-bisabolol as their main component. Our results showed that crude oils of Brazilian plants, specifically E. erythropappus, P. barbatus, and P. amboinicus and its components, could be used as a tool for the developing novel and more efficacious antimicrobial agents.
Assuntos
Anti-Infecciosos/farmacologia , Asteraceae/metabolismo , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Plectranthus/metabolismo , Anti-Infecciosos/análise , Anti-Infecciosos/química , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Brasil , Cromatografia Gasosa-Espectrometria de Massas , Testes de Sensibilidade Microbiana , Óleos Voláteis/análise , Óleos Voláteis/química , Folhas de Planta/metabolismo , Óleos de Plantas/análise , Óleos de Plantas/química , Leveduras/efeitos dos fármacos , Leveduras/crescimento & desenvolvimentoRESUMO
Lung cancer is the leading cause of cancer deaths in the world. Disease stage is the most relevant factor influencing mortality. Unfortunately, most patients are still diagnosed at an advanced stage and their five-year survival rate is only 4%. Thus, it is relevant to identify novel drugs that can improve the treatment options for lung cancer. Natural products have been an important source for the discovery of new compounds with pharmacological potential including antineoplastic agents. We have previously isolated a prenylated benzophenone (7-epiclusianone) from Garcinia brasiliensis (Clusiaceae) that has several biological properties including antiproliferative activity against cancer cell lines. In continuation with our studies, the present work aimed to investigate the mechanisms involved with antiproliferative activity of 7-epiclusianone in A549 cells. Our data showed that 7-epiclusianone reduced the viability of A549 cells in a concentration-dependent manner (IC50 of 16.13 ± 1.12 µM). Cells were arrested in G1/S transition and apoptosis was induced. In addition, we observed morphological changes with cytoskeleton disorganization in consequence of the treatment. Taken together, the results showed that cell cycle arrest in G1/S transition is the main mechanism involved with antiproliferative activity of 7-epiclusianone. Our results are promising and open up the prospect of using this compound in further anticancer in vivo studies.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Benzofenonas/farmacologia , Benzoquinonas/farmacologia , Células Epiteliais/efeitos dos fármacos , Frutas/química , Garcinia/química , Mucosa Respiratória/efeitos dos fármacos , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Benzofenonas/química , Benzofenonas/isolamento & purificação , Benzoquinonas/química , Benzoquinonas/isolamento & purificação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/ultraestrutura , Células Epiteliais/metabolismo , Células Epiteliais/ultraestrutura , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Extratos Vegetais/química , Mucosa Respiratória/metabolismo , Mucosa Respiratória/ultraestruturaRESUMO
CONTEXT: Nectandra (Lauraceae) species have been used in folk medicine as an antidiarrheal, analgesic, antifungal, etc., and have many pharmacological proprieties. OBJECTIVE: Investigation of the chemical composition and cytotoxicity of essential oil from Nectandra leucantha Nees & Mart. leaves. This is the first study involving N. leucantha reported in the literature. MATERIAL AND METHODS: The essential oil of N. leucantha leaves was obtained by hydrodistillation. Its chemical composition was determined using a combination of GC/FID, GC/MS, and determination of Kovats index (KI). In vitro cytotoxic activity was evaluated against six cancer cell lines - murine melanoma (B16F10-Nex2), human glioblastome (U-87), human cervical carcinoma (HeLa), human colon carcinoma (HCT), human breast adenocarcinoma (MCF7), and human cervical tumor (Siha) as well as against one non-tumorigenic cell line - human foreskin fibroblast (HFF). RESULTS: Thirty-three compounds were identified primarily sesquiterpenes (81.41%), the main compounds being bicyclogermacrene (28.44%), germacrene A (7.34%), spathulenol (5.82%), and globulol (5.25%). Furthermore, monoterpenes were also found in the analyzed oil (12.84%), predominantly α- and ß-pinenes (6.59 and 4.57%, respectively). The crude essential oil displayed significant cytotoxic activity against B16F10-Nex2 (IC50 33 ± 1 µg/mL) and U87 (IC50 75.95 ± 0.03 µg/mL) and HeLa (IC50 60 ± 12 µg/mL) cell lines. The main identified compound, bicyclogermacrene, displayed IC50 ranging from 3.1 ± 0.2 to 21 ± 6 µg/mL. DISCUSSION AND CONCLUSION: The results indicate that the crude oils from leaves of N. leucantha displayed cytotoxic activity being bicyclogermacrene, the main compound identified in the crude oil responsible, at least in part, for this potential.
Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Lauraceae/química , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Compostos Bicíclicos com Pontes/química , Compostos Bicíclicos com Pontes/isolamento & purificação , Compostos Bicíclicos com Pontes/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Camundongos , Estrutura Molecular , Óleos Voláteis/isolamento & purificação , Folhas de Planta/química , Óleos de Plantas/isolamento & purificação , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/isolamento & purificação , Sesquiterpenos de Germacrano/farmacologiaRESUMO
Bioactivity-guided fractionation of an antimicrobial active extract from twigs of Baccharis retusa C. DC. (Asteraceae) yielded the flavanone 5,4'-dihydroxy-7-methoxy-flavanone (sakuranetin) as responsible for the detected activity. The structure of the bioactive compound was established on the basis of spectroscopic data analysis, including NMR and MS. Additionally, the structure of a new crystal form of sakuranetin was confirmed by X-ray diffratometry. The minimum inhibitory concentrations (MIC) of isolated compound were determined against pathogenic yeast belonging to the genus Candida (six species), Cryptococcus (two species/four serotypes) and S. cerevisiae BY 4742 (S288c background) and ranged from 0.32 to 0.63 µg/µL. Our results showed that sakuranetin, which structure was fully characterized, could be used as a tool for the design of novel and more efficacious antifungal agents.
Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Asteraceae/química , Flavonoides/química , Flavonoides/farmacologia , Candida/efeitos dos fármacos , Cryptococcus/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Saccharomyces cerevisiae/efeitos dos fármacosRESUMO
Endophytic fungi residing symbiotically in plant tissues are promising sources of bioactive natural products. This study explored the anti-inflammatory potential of an endophytic fungus isolated from the Brazilian medicinal plant Poincianella pluviosa (Sibipiruna). The extract from the endophyte FPD13 exhibited potential ex vivo anti-inflammatory effects by inhibiting prostaglandin E2 (PGE2) release by 75.22%. Phytochemical analysis using High-Performance Liquid Chromatography (HPLC), Nuclear Magnetic Resonance (NMR), and Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS) enabled the isolation and identification of three compounds, including the macrolide Nigrosporolide, the phenyl-propanol Tyrosol, and the terpene Decarestrictine A. Morphological characteristics and Internal Transcribed Spacers region (ITS) sequencing classified fungus FPD13 as Nigrospora zimmermanii. The results reveal the anti-inflammatory potential and chemical diversity of P. pluviosa endophytes, warranting further investigation into the bioactivity and structure elucidation of their bioactive metabolites.
RESUMO
Owing to the potentially harmful adverse effects of current anti-inflammatory drugs, there is a need to identify new alternative substances. Thus, this study aimed to perform a phytochemical analysis of A. polyphylla to identify compounds responsible for its anti-inflammatory activity. Several fractions of the A. polyphylla extract were obtained and evaluated in an ex vivo anti-inflammatory assay using fresh human blood. Among the evaluated fractions, the BH fraction displayed the highest percentage of PGE2 inhibition (74.8%) compared to the reference drugs dexamethasone and indomethacin, demonstrating its excellent potential for anti-inflammatory activity. Astragalin (P1), a known 3-O-glucoside of kaempferol, was isolated from the A. polyphylla extract for the first time. In addition, a new compound (P2) was isolated and identified as the apigenin-3-C-glycosylated flavonoid. Astragalin showed moderate PGE2 activity (48.3%), whereas P2 was not anti-inflammatory. This study contributes to the phytochemical studies of A. polyphylla and confirms its anti-inflammatory potential.
Assuntos
Acacia , Fabaceae , Humanos , Flavonoides/farmacologia , Flavonoides/química , Apigenina/farmacologia , Anti-Inflamatórios/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Fabaceae/química , Compostos FitoquímicosRESUMO
The Croton genus (Euphorbiaceae) is recognized as a promising source for identifying bioactive compounds with antiproliferative activity. However, knowledge on the chemical composition and activity of Croton floribundus, Croton echinocarpus, and Croton zehntneri is limited. Thus, this study aimed to investigate the antiproliferative activity of these species on cells derived from tumoral breast, lung, and melanoma cells, and primary fibroblasts derived from human skin. Metabolomic strategies were applied via ultra-performance liquid chromatography coupled with high-resolution mass spectrometry and multivariate statistical analysis to target the main active compound. The C. floribundus leaf extract exhibited the highest activity, with an IC50 value lower than that of the reference drug - temozolomide - in the most responsive cell line - SK-MEL-147 - and in all the evaluated melanoma cell lines (SK-MEL-147, CHL-1 and WM-1366). Four tetrahydrofurofuran lignans were isolated for the first time from the most promising fraction of the C. floribundus extract. According to the metabolomic and multivariate statistical analyses, the isolated lignan epi-yangambin constituted the main antiproliferative compound against SK-MEL-147; furthermore, it exhibited selective antiproliferative activity for this cell line (IC50 = 13.09 µg/mL and selectivity index = 3.82; temozolomide, IC50 = 121.50 µg/mL) due to, at least in part, its ability to inhibit cell cycle progression at G2/M. This is especially relevant considering the high resistance of melanoma cells to available drugs. Thus, epi-yangambin can serve as a prototype for further antiproliferative investigations.
Assuntos
Antineoplásicos Fitogênicos , Croton , Lignanas , Melanoma , Metabolômica , Folhas de Planta , Humanos , Linhagem Celular Tumoral , Melanoma/tratamento farmacológico , Croton/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Lignanas/farmacologia , Lignanas/isolamento & purificação , Folhas de Planta/química , Estrutura Molecular , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Proliferação de Células/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Furanos/farmacologia , Furanos/isolamento & purificaçãoRESUMO
Parkinson's disease (PD) is a neurodegenerative disorder characterized by diverse symptoms, where accurate diagnosis remains challenging. Traditional clinical observation methods often result in misdiagnosis, highlighting the need for biomarker-based diagnostic approaches. This study utilizes ultraperformance liquid chromatography coupled to an electrospray ionization source and quadrupole time-of-flight untargeted metabolomics combined with biochemometrics to identify novel serum biomarkers for PD. Analyzing a Brazilian cohort of serum samples from 39 PD patients and 15 healthy controls, we identified 15 metabolites significantly associated with PD, with 11 reported as potential biomarkers for the first time. Key disrupted metabolic pathways include caffeine metabolism, arachidonic acid metabolism, and primary bile acid biosynthesis. Our machine learning model demonstrated high accuracy, with the Rotation Forest boosting model achieving 94.1% accuracy in distinguishing PD patients from controls. It is based on three new PD biomarkers (downregulated: 1-lyso-2-arachidonoyl-phosphatidate and hypoxanthine and upregulated: ferulic acid) and surpasses the general 80% diagnostic accuracy obtained from initial clinical evaluations conducted by specialists. Besides, this machine learning model based on a decision tree allowed for visual and easy interpretability of affected metabolites in PD patients. These findings could improve the detection and monitoring of PD, paving the way for more precise diagnostics and therapeutic interventions. Our research emphasizes the critical role of metabolomics and machine learning in advancing our understanding of the chemical profile of neurodegenerative diseases.
RESUMO
Casearia sylvestris (Salicaceae), popularly known as "guaçatonga", is a plant widely used in folk medicine to treat various diseases, including cancer. The present work deals with the chemical composition as well as the cytotoxic evaluation of its essential oil, its main constituent and derivatives. Thus, the crude essential oil from leaves of C. sylvestris was obtained using a Clevenger type apparatus and analyzed by GC/MS. This analysis afforded the identification of 23 substances, 13 of which corresponded to 98.73% of the total oil composition, with sesquiterpene a-zingiberene accounting for 50% of the oil. The essential oil was evaluated for cytotoxic activity against several tumor cell lines, giving IC50 values ranging from 12 to 153 mg/mL. Pure a-zingiberene, isolated from essential oil, was also evaluated against the tumor cell lines showing activity for HeLa, U-87, Siha and HL60 cell lines, but with IC50 values higher than those determined for the crude essential oil. Aiming to evaluate the effect of the double bonds of a-zingiberene on the cytotoxic activity, partially hydrogenated a-zingiberene (PHZ) and fully hydrogenated a-zingiberene (THZ) derivatives were obtained. For the partially hydrogenated derivative only cytotoxic activity to the B16F10-Nex2 cell line (IC50 65 mg/mL) was detected, while totally hydrogenated derivative showed cytotoxic activity for almost all cell lines, with B16F10-Nex2 and MCF-7 as exceptions and with IC50 values ranging from 34 to 65 mg/mL. These results indicate that cytotoxic activity is related with the state of oxidation of compound.