RESUMO
Pt(II) and Pd(II) coordinating N-donor ligands have been extensively studied as anticancer agents after the success of cisplatin. In this work, a novel bidentate N-donor ligand, the N-[[4-(phenylmethoxy)phenyl]methyl]-2-pyridinemethanamine, was designed to explore the antiparasitic, antiviral and antitumor activity of its Pt(II) and Pd(II) complexes. Chemical and spectroscopic characterization confirm the formation of [MLCl2 ] complexes, where M=Pt(II) and Pd(II). Single crystal X-ray diffraction confirmed a square-planar geometry for the Pd(II) complex. Spectroscopic characterization of the Pt(II) complex suggests a similar structure. 1 H NMR, 195 Pt NMR and HR-ESI-MS(+) analysis of DMSO solution of complexes indicated that both compounds exchange the chloride trans to the pyridine for a solvent molecule with different reaction rates. The ligand and the two complexes were tested for inâ vitro antitumoral, antileishmanial, and antiviral activity. The Pt(II) complex resulted in a GI50 of 10.5â µM against the NCI/ADR-RES (multidrug-resistant ovarian carcinoma) cell line. The ligand and the Pd(II) complex showed good anti-SARS-CoV-2 activity with around 65 % reduction in viral replication at a concentration of 50â µM.
Assuntos
Antineoplásicos , Complexos de Coordenação , Platina/farmacologia , Platina/química , Ligantes , Cisplatino , Antineoplásicos/farmacologia , Antineoplásicos/química , Antivirais/farmacologia , Paládio/farmacologia , Paládio/química , Cristalografia por Raios X , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Linhagem Celular TumoralRESUMO
Palicourea species has been used in folk medicine in the treatment of some diseases including cancer and inflammatory disorders. This work aimed to evaluate the in vitro antiproliferative and in vivo topical anti-inflammatory activities of the methanolic extract, fractions and two major alkaloids isolated from Palicourea minutiflora. Methanolic extract, non-alkaloidal and alkaloidal fractions exhibited strong growth inhibition for ovarian cell lines (OVCAR-3, GI50 = 3.8 at 16.3 µg mL-1) and the vincosamide alkaloid revealed selective effect on the growth of glioma cell lines (U251, GI50 = 33.0 µg mL-1) compared with doxorubicin (DOX, GI50 = 0.42 and 0.025 µg mL-1, respectively) anticancer drug. Methanolic extract, fractions and strictosidinic acid showed significant inhibitory effect with 62.7% at 77.5% (p < 0.05) to ear edema induced by croton oil and 81% at 100% (p < 0.05) to myeloperoxidase assay compared with indomethacin (positive control) 68.4% and 91.3% (p < 0.05), respectively.
Assuntos
Alcaloides , Neoplasias Ovarianas , Rubiaceae , Alcaloides/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Edema/induzido quimicamente , Edema/tratamento farmacológico , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
The aerial parts of L. cultratus were submitted to a phytopharmacological investigation in order to isolate and identify the major secondary metabolites and evaluate its crude extract, fractions and isolated compounds for antiproliferative activity. Seven compounds were isolated and identified as the chalcones 2',4'-dihydroxy-5'-prenylchalcone (1) and isocordoin (2), the flavanone 8-prenylpinocembrin (3), the alkaloid 4-hydroxy-N-methylproline (4), the triterpenes lupeol and lupenone. These compounds were identified by nuclear magnetic resonance of 1H and 13C data in comparison with literature. Hexanic fraction and chalcone 2',4'-dihydroxy-5'-prenylchalcone showed potent results against human cancer cell lines tested.
Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Fabaceae/química , Catecóis/química , Catecóis/farmacologia , Proliferação de Células/efeitos dos fármacos , Chalconas/química , Chalconas/isolamento & purificação , Chalconas/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Fabaceae/metabolismo , Humanos , Células K562 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Plantas Medicinais/metabolismo , Metabolismo Secundário , Triterpenos/química , Triterpenos/farmacologiaRESUMO
Glioblastoma (GBM) is the most frequent and highest-grade brain tumor in adults. The prognosis is still poor despite the use of combined therapy involving maximal surgical resection, radiotherapy, and chemotherapy. The development of more efficient drugs without noticeable side effects is urgent. Coronarin D is a diterpene obtained from the rhizome extract of Hedychium coronarium, classified as a labdane with several biological activities, principally anticancer potential. The aim of the present study was to determine the anti-cancer properties of Coronarin D in the glioblastoma cell line and further elucidate the underlying molecular mechanisms. Coronarin D potently suppressed cell viability in glioblastoma U-251 cell line, and also induced G1 arrest by reducing p21 protein and histone H2AX phosphorylation, leading to DNA damage and apoptosis. Further studies showed that Coronarin D increased the production of reactive oxygen species, lead to mitochondrial membrane potential depolarization, and subsequently activated caspases and ERK phosphorylation, major mechanisms involved in apoptosis. To our knowledge, this is the first analysis referring to this compound on the glioma cell line. These findings highlight the antiproliferative activity of Coronarin D against glioblastoma cell line U-251 and provide a basis for further investigation on its antineoplastic activity on brain cancer.
Assuntos
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Diterpenos/farmacologia , Glioblastoma/tratamento farmacológico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/química , Glioblastoma/patologia , Humanos , Fosforilação/efeitos dos fármacos , Espécies Reativas de Oxigênio/química , Zingiberaceae/químicaRESUMO
The phytochemical investigation of Grazielia gaudichaudeana aerial parts yielded 15 compounds, including diterpenes, triterpenes, sterols and flavonoids. With exception to ent-kaurenoic acid diterpenes, the compounds isolated are being described for the first time in this species. Some unusual 1 H-NMR chemical shifts of 18-nor-ent-labdane (7-9) led us carry out a conformational analysis by theoretical calculations in order to support the experimental data. Moreover, due to the limitation of studies focused on pharmacological potential of Grazielia gaudichaudeana, the present study was carried out to investigate the antioxidant, antiproliferative, antiviral, antileishmanial and antimicrobial activities from the extract, fractions and isolated compounds obtained from this species. Ethyl acetate fraction showed significant activity in the antiproliferative assay, with GI50 range of 3.9 to 27.2â µg mL-1 . Dichloromethane fraction, rich in diterpenoids, inhibited all human tumor cell lines tested, and the nor-labdane 7 showed potent cytotoxic activity against glioma and ovary cancer cell lines.
Assuntos
Asteraceae/química , Diterpenos/química , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/química , Antiprotozoários/química , Antiprotozoários/isolamento & purificação , Antiprotozoários/farmacologia , Asteraceae/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Fungos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Leishmania/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Conformação Molecular , Extratos Vegetais/químicaRESUMO
BACKGROUND: The genus Psychotria and Palicourea are reported as a source of alkaloids and iridoids, which exhibit biological activities. This study aimed to evaluate antiproliferative and anticholinesterase activities and quantification of the alkaloids of seven species among the genus found in Mato Grosso do Sul region in Brazil. METHODS: Concentrations of alkaloids were measured spectrophotometrically. The extracts were submitted to antiproliferative activity against ten cell lines. The anticholinesterase activity of the extracts was developed using brain structures of male Wistar rats: cerebral cortex, hippocampus, hypothalamus and striatum by the Ellman method. RESULTS: Alkaloids from Psychotria and Palicourea species were quantified which showed values of 47.6 to 21.9 µg/g. Regarding the antiproliferative potential, Palicourea crocea demonstrated selectivity against the 786-0 cell line (GI50: 22.87 µg/mL). Psychotria leiocarpa inhibited cell growth against OVCAR-3 (GI50: 3.28 µg/mL), K-562 (GI50: 5.26 µg/mL), HaCaT (GI50: 27.20 µg/mL), PC-3 (GI50: 34.92 µg/mL), MCF-7 (GI50: 35.80 µg/mL) and P. capillacea showed activity against OVCAR-3 (GI50: 2.33 µg/ml) and U251 (GI50: 16.66 µg/ml). The effect of acetylcholinesterase inhibition was more effective in the hippocampus, demonstrating inhibition for Paliourea crocea, Psychotria deflexa, P. brachybotrya and P. leiocarpa of 70%, 57%, 50% and 40%, respectively, followed by P. poeppigiana and P. capillacea, inhibiting 21%, compared to the control. CONCLUSION: Herein, the present work showed for the first time, anticholinesterasic and antiproliferative activities of extracts of Palicourea and Psychotria seem to be mainly associated with the levels of alkaloids in the leaves of these species.
Assuntos
Alcaloides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Inibidores da Colinesterase/farmacologia , Iridoides/farmacologia , Extratos Vegetais/farmacologia , Rubiaceae/química , Alcaloides/isolamento & purificação , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Brasil , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Inibidores da Colinesterase/isolamento & purificação , Hipocampo/efeitos dos fármacos , Hipocampo/enzimologia , Humanos , Iridoides/isolamento & purificação , Masculino , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Ratos , Ratos Wistar , Rubiaceae/crescimento & desenvolvimento , Especificidade da EspécieRESUMO
BACKGROUND: Trichilia silvatica, popularly known as "catiguá-branco", is distributed in Brazil (Mato Grosso do Sul), and members of this genus are commonly used for the treatment of rheumatism (arthritis). The aim of this research was to investigate the anti-inflammatory, antioxidant and antiproliferative activities of the methanolic extract of the leaves (MEL-TS) and bark (MEB-TS) of T. silvatica. We also evaluated the concentration of phenolic compounds, flavonoids, flavonol, and condensed tannins by liquid chromatography - photodiode array (LC/PDA) analysis. METHODS: The MEL-TS and MEB-TS revealed the presence of caffeic acid in both extracts by LC/PDA. The samples were evaluated for antioxidant activity using free-radical scavenging and lipoperoxidation assays. The anti-inflammatory effects were studied in carrageenan-induced paw edema, pleurisy and zymosan-induced arthritis. RESULTS: The MEL-TS and MEB-TS showed the total phenolic concentration (270.8 ± 17.10 mg gallic acid equivalents GAE/g extract and 278.8 ± 25.13 mg GAE/ g extract, respectively), and flavonoids in MEL-TS (209.30 ± 2.91 mg quercetin equivalents QE/ g extract). In the lipoperoxidation assay, exhibited moderate antioxidant activity with IC50 values ≤ 35.32 µg/mL. Both extracts inhibited oedema induced by carrageenan at 2 h and 4 h, inhibited leukocyte migration at 6 h post administration, and did not impact zymosan-induced arthritis. Finally, MEL-TS was particularly effective against prostate cell line (GI50 ≤ 0.22 µg/mL). CONCLUSION: Overall, the results indicated that T. silvatica reduce migration leukocytes activity, edema formation in these models of experimental arthritis could explain the popular use for treatment of inflammatory processes (rheumatism).
Assuntos
Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Meliaceae/química , Extratos Vegetais/isolamento & purificação , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Compostos de Bifenilo/química , Brasil , Linhagem Celular Tumoral , Edema/tratamento farmacológico , Feminino , Radicais Livres/química , Humanos , Masculino , Meliaceae/crescimento & desenvolvimento , Camundongos , Picratos/química , Casca de Planta/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Pleurisia/tratamento farmacológicoRESUMO
The bis-(1,10-phenanthroline)copper(I) complex, [Cu(I)(phen)2]+, was the first copper-based artificial nuclease reported in the literature. The biological and ligand-like properties of sulfonamides make them good candidates for fine-tuning the reactivity of the [Cu(phen)2] motif with biomolecules. In this context, we developed three novel copper(II) complexes containing the sulfonamides sulfameter (smtrH) and sulfadimethoxine (sdmxH) and (N^N)-bidentate ligands (2,2'-biyridine or 1,10-phenantroline). The compounds were characterized by chemical and spectroscopic techniques and single-crystal X-ray crystallography. When targeting plasmid DNA, the phen-containing compounds [Cu(smtr-)2(phen)] (1) and [Cu(sdmx-)2(phen)] (2) demonstrated nuclease activity even in the absence of reducing agents. Addition of ascorbic acid resulted in a complete cleavage of DNA by 1 and 2 at concentrations higher than 10⯵M. Experiments designed to evaluate the copper intermediates involved in the nuclease effect after reaction with ascorbic acid identified at least the [Cu(I)(N^N)2]+, [Cu(I)(sulfa)(N^N)]+ and [Cu(I)(sulfa)2]+ species. The compounds interact with DNA via groove binding and intercalation as verified by fluorescence spectroscopy, circular dichroism (CD) and molecular docking. The magnitude and preferred mode of binding are dependent on the nature of both N^N ligand and the sulfonamide. The potent nuclease activity of compounds 1 and 2 are well correlated with their antiproliferative and anti-M. tuberculosis profiles. The results presented here demonstrated the potential for further development of copper(II)-sulfonamide-(N^N) complexes as multipurpose metallodrugs.
Assuntos
Antituberculosos , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação , Cobre , Desoxirribonucleases , Mycobacterium tuberculosis/crescimento & desenvolvimento , Sulfonamidas , Antituberculosos/síntese química , Antituberculosos/química , Antituberculosos/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Cobre/química , Cobre/farmacologia , Clivagem do DNA/efeitos dos fármacos , Desoxirribonucleases/síntese química , Desoxirribonucleases/química , Desoxirribonucleases/farmacologia , Humanos , Células K562 , Células MCF-7 , Simulação de Acoplamento Molecular , Sulfonamidas/química , Sulfonamidas/farmacologiaRESUMO
Myrcia bella Cambess., Myrcia fallax (Rich.) DC. and Myrcia guianensis (Aubl.) DC. (Myrtaceae) are trees found in Brazilian Cerrado. They have been widely used in folk medicine for the treatment of gastrointestinal disorders, hemorrhagic and infectious diseases. Few reports have been found in the literature connecting their phenolic composition and biological activities. In this regard, we have profiled the main phenolic constituents of Myrcia spp. leaves extracts by ESI(−)Q-TOF-MS. The main constituents found were ellagic acid (M. bella), galloyl glucose isomers (M. guianensis) and hexahydroxydiphenic (HHDP) acid derivatives (M. fallax). In addition, quercetin and myricetin derivatives were also found in all Myrcia spp. extracts. The most promising antioxidant activity, measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity, was found for M. fallax extracts (EC50 8.61 ± 0.22 µg·mL−1), being slightly less active than quercetin and gallic acid (EC50 2.96 ± 0.17 and 2.03 ± 0.02 µg·mL−1, respectively). For in vitro antiproliferative activity, M. guianensis showed good activity against leukemia (K562 TGI = 7.45 µg·mL−1). The best antimicrobial activity was observed for M. bella and M. fallax to Escherichia coli (300 and 250 µg·mL−1, respectively). In conclusion, the activities found are closely related to the phenolic composition of these plants.
Assuntos
Anti-Infecciosos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Myrtaceae/química , Extratos Vegetais/farmacologia , Anti-Infecciosos/química , Antineoplásicos Fitogênicos/química , Antioxidantes/química , Linhagem Celular Tumoral , Sinergismo Farmacológico , Flavonóis/química , Flavonóis/farmacologia , Humanos , Redes e Vias Metabólicas , Testes de Sensibilidade Microbiana , Fenóis/química , Fenóis/farmacologia , Extratos Vegetais/química , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
The crude extract and fractions from the branches of Ixora brevifolia, a tree found in the Brazilian Cerrado, were tested for anti-inflammatory and in vitro antiproliferative effects. The crude extract and n-hexane fraction exhibited significant inhibition of ear oedema in mice, while n-hexane-precipitated and chloroform fractions strongly inhibited the myeloperoxidase activity in ear tissue. The n-hexane and n-hexane-precipitated fractions showed strong growth inhibition for glioma cell line and the hydromethanolic fraction inhibited the growth of leukaemia cell line.