ABSTRACT
OBJECTIVES: The aim of this study was to investigate the cytotoxic effect of new 1,4-naphthoquinone- 1,2,3-triazoles, named C2 to C8 triazole derivatives, towards human cancer cell lines. METHODS: The effect on cell viability was assessed by MTT and propidium iodide assays. The cytotoxic effect of C2 and C3 in K562 and HL-60 cells were analyzed by flow cytometry, DNA fragmentation and reactive oxygen species (ROS) production. Western blot and q-PCR procedures were also performed. KEY FINDINGS: C2 and C3 inhibited both K562 and HL-60 cells growth in a concentration-dependent manner. C2 presented the highest cytotoxic activity with an IC50 of approximately 14 µm and 41 µm for HL-60 and K562 cells, respectively, while being less toxic to normal peripheral blood monocyte cells. Both derivatives induced cellular changes in HL-60 cells, characteristic of apoptosis, such as mitochondrial membrane depolarization, phosphatidylserine externalization, increasing sub-G1 phase, DNA fragmentation, downregulating Bcl-2 protein and upregulating Bax protein. In K562 cells, C2 and C3 induced S-phase arrest of cell cycle, which was associated with upregulation of p21. The effect of these derivatives in HL-60 cells can be related to the ROS intracellular level. CONCLUSION: Taken together our results showed that C2 and C3 triazole derivatives presented the best potential for drug design.
Subject(s)
Antineoplastic Agents/pharmacology , Leukemia/drug therapy , Naphthoquinones/pharmacology , Triazoles/pharmacology , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Apoptosis Regulatory Proteins/metabolism , Cell Cycle Proteins/metabolism , Cell Proliferation/drug effects , Cell Survival/drug effects , DNA Fragmentation , Dose-Response Relationship, Drug , HL-60 Cells , Humans , Inhibitory Concentration 50 , K562 Cells , Leukemia/metabolism , Leukemia/pathology , Membrane Potential, Mitochondrial/drug effects , Molecular Structure , Naphthoquinones/chemistry , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , S Phase Cell Cycle Checkpoints/drug effects , Structure-Activity Relationship , Triazoles/chemistryABSTRACT
The paper is a review of the literature on the ethnobotanical, chemical and pharmacological aspects of the species Cissampelos sympodialis Eichler, Menispermaceae, in order to assess its potential for the treatment of asthma. The aqueous infusion from the leaves of this Brazilian plant is used in the traditional medicine for the treatment of respiratory conditions, including colds, bronchitis and asthma. A multidisciplinary approach has led to the elucidation of the main chemical biomarkers and of the mechanism of action of the extract and its isolated constituents in animal models of inflammation and asthma. A comprehensive review of the literature on the species and its related chemical constituents was conducted using Pubmed, Web of Sciences, Lilacs, SciFinder, as well as conference proceedings. Retrieved literature data demonstrates that the aqueous fraction of the ethanolic extract from the leaves exerts an immunomodulatory activity in different animal models of asthma. This include an increase in the levels of anti-inflammatory cytokines, a decrease in the production of antigen-specific immunoglobulin, a decrease in mucus production and deposition in the airways, and a direct bronchodilator activity. These preclinical results clearly demonstrate the potential of this species for the treatment of asthma and points to the need for well-designed clinical trials to finally validate the traditional use of this herbal medicine.
ABSTRACT
The usefulness of pyrolysis coupled to gas chromatography/mass spectrometry (Py-GC/MS) to evaluate the identity and reproducibility of different brands and batches of commercially available samples of Cymbopogon citratus Stapf (sold as tea) was investigated. Samples of the vegetable material were extracted using hexane and the extract was pyrolysed at 450 ºC using a vertical microfurnace pyrolyser interfaced directly with a gas chromatograph/mass spectrometer operated using electron impact ionization at 70 eV. The relative peak areas of the different compounds identified on the pyrograms were used for multivariate data analysis using principal component analysis (PCA) and hierarchical cluster analysis (HCA) techniques. Principal component analysis of pyrolysis data from samples of different brands was able to represent 84.7 percent of the total variability within the first two principal components, and led to the correct classification of the samples tested. The method was also able to reveal important differences between samples when different batches of the same brand were compared.
A utilidade da técnica de pirólise acoplada à cromatografia à gás/espectrometria de massas (Py-GC/MS) na avaliação da identidade e reprodutibilidade de diferentes marcas e lotes de amostras comerciais de Cymbopogon citratus Stapf. (comercializado como chá) foi investigada. Amostras do material vegetal foram extraídas com hexano e o extrato foi diretamente pirolisado a 450 ºC utilizando um pirolisador de microforno vertical, interfaciado diretamente com um cromatógrafo à gás/espectrômetro de massas, operado utilizando ionização por impacto eletrônico a 70 eV. As áreas relatives dos picos de interesse identificados nos pirogramas foram utilizadas para análise estatística multivariada, com análise de componentes principais e análise hierárquica de agrupamentos. A análise de components principais dos dados de pirólise foi capaz de representar 84.7 por cento da variabilidade total nos dois primeiros componentes calculados e levou a correta classificação das amostras testadas. O método foi capaz de revelar diferenças importantes entre amostras, quando diferentes lotes da mesma marca foram comparados.