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The development of novel phytotoxic compounds has been an important aim of weed control research. In this study, we synthesized fluorinated chalcone derivatives featuring both electron-donating and electron-withdrawing groups. These compounds were evaluated both as inhibitors of the photosystem II (PSII) electron chain as well as inhibitors of the germination and seedling growth of Amaranthus plants. Chlorophyll a (Chl a) fluorescence assay was employed to evaluate their effects on PSII, while germination experiments were conducted to assess their impact on germination and seedling development. The results revealed promising herbicidal activity for (E)-3-(4-bromophenyl)-1-(4-fluorophenyl)prop-2-en-1-one (7 a) and (E)-1-(4-fluorophenyl)-3-phenylprop-2-en-1-one (7 e). Compounds 7 a and 7 e exhibited a reduction in Chl a parameters associated with performance indexes and electron transport per reaction center. This reduction suggests a decrease in PSII activity, attributed to the blockage of electron flow at the quinone pool. Molecular docking analyses of chalcone derivatives with the D1 protein of PSII revealed a stable binding conformation, wherein the carbonyl and fluorine groups interacted with Phe265 and His215 residues, respectively. Additionally, at a concentration of 100 µM, compound 7 e demonstrated pre- and post-emergent herbicidal activity, resulting in a reduction of the seed germination index, radicle and hypocotyl lengths of Amaranthus weeds.

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A família de inibidores de crescimento (inhibitor of growth - ING) corresponde a um grupo de genes supressores tumorais cuja expressão se apresenta alterada ou ausente em diversos tipos de câncer. Os produtos destes genes estão relacionados, principalmente, a processos celulares indispensáveis na carcinogênese, como remodelação da cromatina, proliferação celular, replicação e reparo do DNA. Este estudo avaliou a expressão imuno-histoquímica da proteína ING3 em 45 espécimes de queilite actínica (QA) e 48 espécimes de carcinoma de células escamosas de lábio inferior (CCELI). A expressão da proteína foi comparada entre os dois grupos de amostras, bem como com os parâmetros clínico-patológicos das lesões estudadas, através dos testes estatísticos Exato de Fisher, Kruskal-Wallis (KW), Mann-Whitney (U) e teste de correlação de Spearman. Um nível de significância de 5% foi adotado para todos os testes, sendo considerados significativos os valores de p ≤ 0,05. Não foram encontradas associações estatisticamente significativas entre as variáveis morfológicas de CCELI e tamanho do tumor, envolvimento linfonodal, estadiamento clínico, recorrência local e metástase linfonodal após tratamento (p>0,05). Óbitos foram significativamente mais frequentes em tumores de alto escore de risco histopatológico (p<0,05). Nas QAs, diferenças significativas na expressão de ING3 núcleo-citoplasmática, e restrita ao citoplasma, com a gradação de Kujan et al. (2006) foram encontradas (p<0,05). Nos CCELIs, não houve diferença estatisticamente significativa ao comparar as expressões de ING3 (núcleo-citoplasmática e restrita ao citoplasma) com os parâmetros clínicos e morfológicos (p>0,05). A expressão de ING3 núcleo-citoplasmática foi significativamente menor em CCELI quando comparada aos casos de QA (p<0,05) e a expressão restrita ao citoplasma foi significativamente maior nos CCELIs (p<0,05). Nossos resultados sugerem que há notável diminuição da expressão nuclear de ING3 conforme a progressão maligna, indicando função supressora tumoral prejudicada desta proteína em QAs e CCELIs. Entretanto, acredita-se que, na carcinogênese labial, ING3 caracteriza-se melhor como um marcador preditor de transformação maligna, do que um biomarcador de comportamento biológico tumoral (AU).

The family of inhibitors of growth (ING) corresponds to a group of tumor suppressor genes whose expression is altered or absent in several types of cancer. The products of these genes are mainly related to cellular processes indispensable in carcinogenesis, including cell proliferation, DNA replication and repair. This study evaluated the immunohistochemical expression of ING3 protein in 45 actinic cheilitis (AC) and 48 lower lip squamous cell carcinoma (CCELI) specimens. Protein expression was compared between the two groups of samples, as well as with the clinicopathological parameters of studied lesions, using Fisher's exact tests, Kruskal-Wallis (KW), Mann-Whitney (U) and correlation test of Spearman. A significance level of 5% was adopted for all tests, with values of p ≤ 0.05 being considered significant. No statistically significant associations were found between morphological variables of CCELI and tumor size, lymph node involvement, clinical staging, local recurrence and lymph node metastasis after treatment (p>0.05). Deaths were significantly more frequent in tumors with a high histopathological risk score (p<0.05). In ACs, significant differences in nuclear-cytoplasmic and restricted to the cytoplasm expression of ING3, with gradation of Kujan et al. (2006) were found (p<0.05). In CCELIs, there was no statistically significant difference when comparing ING3 expressions (nucleocytoplasmic and cytoplasmic restricted) with clinical and morphological parameters (p>0.05). Nucleocytoplasmic ING3 expression was significantly lower in CCELI when compared to AC cases (p<0.05) and cytoplasm-restricted expression was significantly higher in CCELIs (p<0.05). Our results suggest that there is a remarkable decrease in ING3 nuclear expression according to malignant progression, indicating an impaired tumor suppressor function of this protein in AC and CCELI. However, it is believed that, in lip carcinogenesis, ING3 is better characterized as predictive marker of malignant transformation, rather than a biomarker of tumor biological behavior (AU).

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We report the evaluation of chalcone derivatives as photosystem II (PSII) and plant growth inhibitors. Chalcone derivatives were evaluated as PSII inhibitors through Chl a fluorescence measurement. (E)-Chalcone (6a) and (E)-3-(4-bromophenyl)-1-(4-fluorophenyl)prop-2-en-1-one (6j) showed the best results, reducing the performance index on absorption basis parameter (PIabs ) by 70 %. Additionally, the decrease of TR0 /RC and ET0 /RC parameters indicates that the chalcone derivatives limited the number of active PSII reaction centers and the amount of trapped energy within them. Compounds 6a and 6j both act as post-emergent herbicides at 50 µM, reducing the root biomass of the Ipomoea grandifolia weed by 72 % and 83 %, respectively, corroborating the fluorescence results. The selectivity against weeds as compared to valuable crops by compounds 6a and 6j were evaluated employing Zea mays and Phaseolus vulgaris plants. In these, our newly synthesized compounds showed no effects on biomass accumulation of roots and aerial parts when compared to the control, providing valuable evidence for the role of these compounds as selective inhibitors of the growth of undesired weeds.

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Murici (Byrsonima crassifolia (L.) Kunth and B. verbascifolia (L.) DC.) and tapereba (Spondias mombin) are Amazonian fruits that contain bioactive compounds. Biochemical and molecular characterization of these fruits can reveal their potential use in preventing diseases, including cancer. The extracts were characterized regarding the presence and profile of carotenoids by high-performance liquid chromatography (HPLC), total phenolic content by the Folin-Ciocalteu assay, and antioxidant activity by antioxidant value 2,2-diphenyl-1-picrylhydrazyl (DPPH) content analysis, 22,20-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) content analysis, Ferric-Reducing Ability of Plasma (FRAP), and Oxygen Radical Absorbance Capacity (ORAC) analysis. The extracts of tapereba and murici studied were important sources of total carotenoids and lutein, respectively. The extracts were then tested for their effect on the viability of the A2780 ovarian cancer (OC) cell line and its cisplatin (CDDP)-resistant derived cell line, called ACRP, by using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays. Their influence on cell cycle and apoptosis were analyzed by using flow cytometry. Murici and tapereba cell extracts exhibited a strong bioactivity by inhibiting A2780 and ACRP cell viability by 76.37% and 78.37%, respectively, besides modulating the cell cycle and inducing apoptotic cell death. Our results open new perspectives for the development of innovative therapeutic strategies using these Amazon fruit extracts to sensitize ovarian cancer cells to current chemotherapeutic options.

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The effects of different three carbon sources, that is, glucose, fructose, and sucrose, on production, molecular properties and antiproliferative activity of exopolysaccharide (EPS), were evaluated in the submerged culture of Scleroderma areolatum Ehrenb. Among carbon sources examined, the addition of sucrose maximizes the mycelia production, while fructose could maximize the EPS yield. Although the predominant carbohydrate compositions identified were gluconic acid and mannose, the monosaccharide composition of EPSs was also different significantly. FT-IR spectral analysis revealed there was no significant difference among the prominent characteristic groups in three EPSs. The molecular weight of EPSs was also affected by carbon source, being generally lower compared with that with glucose. However, all EPSs molecule existed as nearly globular shape form in aqueous solution. The variation of carbon sources also affected antiproliferative activity examined in vitro using cell proliferation assay. Fructose was optimal carbon source giving higher antiproliferative activity probably due to the relatively high contents of xylose in the EPS with low molecular weight.

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Indole derivatives were synthetized based on the Fischer indole methodology using different phenyl hydrazine hydrochlorides and either cyclohexanone or 2-butanone. The pre- and post-emergent herbicidal activities were evaluated against Ipomoea grandifolia. A carbazole, 6-chloro-2,3,4,9-tetrahydro-1H-carbazole (3b), decreased the PIabs parameter by 32% and increased the cross-section related parameters, indicating the inactivation of the reaction center on photosystem II. Compound 3b acts as a post-emergent herbicide prototype since dry biomass was reduced by 50%, corroborating the fluorescence results. Comparing instead with a germination experiment, 2,3,4,9-tetrahydro-1H-carbazole (3a) was found to be the most effective agent, inhibiting seed germination by 22% and decreasing root length by 50%. The tetrahydrocarbazoles showed better results than indole derivatives potentially due to the presence of methylene groups at structures, which increase the compounds' lipophilicity and may facilitate their access to the plant. In addition, electron withdrawing groups on the aromatic ring were found to correlate with increased herbicide activity. Further optimization of this series towards the development of herbicides is ongoing.

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Proteins from Juglans regia L. were isolated. Then, proteins were hydrolyzed with different enzymes. Antiproliferative activity of proteins and of the protein hydrolysates of J. regia L. were evaluated using the sulforhodamine B method. Glutelin and prolamin proteins presented a high antiproliferative activity against cancer cells PC-3 (prostate) and K-562 (leukemia) with values of 43.9 and 84.4 µg/mL, respectively. The highest inhibitory effect observed was 50% at 0.25 µg/mL concentration in gastrointestinal digestion with pepsin and corolase pp in a dose-dependent manner against cancer cell UACC62 (melanoma). Pepsin hydrolysate showed inhibitory effects against cancer cell UACC62 (melanoma) with a concentration of 71.0 µg/mL. The effects were studied in a dose-dependent manner. The hydrolysate obtained with neutrase enzyme presented inhibitory effects against cancer cell UACC62 (melanoma) at a concentration of 25 µg/mL. Neither proteins nor protein hydrolysates presented cytotoxicity against normal cell assay VERO (epithelial).

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BACKGROUND: A variety of chalcones have demonstrated cytotoxic activity toward several cancer cell lines. This study aimed to investigate the cytotoxicity of four chalcones derivatives of 2-acetylthiophene in human breast cancer cell lines. METHODS: MCF-7 and MDA-MB-231 cells were treated with synthesized chalcones and the cytotoxicity was evaluated by tetrazolium dye (MTT), live/dead, and DAPI assays. RESULTS: Chalcones significantly decreased MCF-7 and MDA-MB-231 cells viability in vitro in a dose dependent manner. After 48h treatment, the IC50 values ranging from 5.52 to 34.23µM. Chalcone 3c displayed the highest cytotoxic activity from all the tested compounds. Cytotoxic effects of compounds were confirmed in the live/dead assay. In addition, DAPI staining revealed that these compounds induce death by apoptosis. CONCLUSION: The data speculate that chalcone derivatives of 2-acetylthiophene may represent a source of therapeutic agents for human breast cancer.

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Harpagophytum procumbens (Hp) has been used as antiinflammatory and analgesic agent for the treatment of rheumatic diseases. The principal active component of Hp is harpagoside (HA). We tested the toxicity of this new therapeutic agent in a hepatic cell line (HepG2/C3A). Hp was found to be cytotoxic, and HA was found to decrease the number of cells in S phase, increase the number of cells in G2/M phase and induce apoptosis. Neither Hp nor HA was genotoxic. The expression of CDK6 and CTP3A4 was reduced by Hp, and both HA and Hp caused a significant reduction of CYP1A2 and CYP3A4 expression. It is possible that the cytotoxicity caused by HA and Hp does not involve transcriptional regulation of the cyclins and CDKs tested but is instead related to the inhibition of metabolism. This is evidenced by the results of an MTT assay and changes in the expression of genes related to drug metabolism, leading to cell death. Indeed, the cells exhibited decreased proliferation upon exposure to Hp and HA. The data show that treatment with either Hp or HA can be cytotoxic, and this should be taken into consideration when balancing the risks and benefits of treatments for rheumatic diseases. Copyright © 2016 John Wiley & Sons, Ltd.

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BACKGROUND: Natural products display numerous therapeutic properties (e.g., antibacterial activity), providing the population with countless benefits. Therefore, the search for novel biologically active, naturally occurring compounds is extremely important. The present paper describes the antibacterial action of the Copaifera langsdorffii oleoresin and ten compounds isolated from this oleoresin against multiresistant bacteria; it also reports the antiproliferative activity of the Copaifera langsdorffii oleoresin and (-)-copalic acid. METHODS: MICs and MBCs were used to determine the antibacterial activity. Time-kill curve assays provided the time that was necessary for the bacteria to die. The Minimum Inhbitory Concentration of Biofilm (CIMB50) of the compounds that displayed the best results was calculated. Cytotoxicity was measured by using the XTT assay. RESULTS: The diterpene (-)-copalic acid was the most active antibacterial and afforded promising Minimum Inhibitory Concentration (MIC) values for most of the tested strains. Determination of the bactericidal kinetics against some bacteria revealed that the bactericidal effect emerged within six hours of incubation for Streptococcus pneumoniae. Concerning the antibiofilm action of this diterpene, its MICB50 was twofold larger than its CBM against S. capitis and S. pneumoniae. The XTT assay helped to evaluate the cytotoxic effect; results are expressed as IC50. The most pronounced antiproliferative effect arose in tumor cell lines treated with (-)-copalic acid; the lowest IC50 value was found for the human glioblastoma cell line. CONCLUSIONS: The diterpene (-)-copalic acid is a potential lead for the development of new selective antimicrobial agents to treat infections caused by Gram-positive multiresistant microorganisms, in both the sessile and planktonic mode. This diterpene is also a good candidate to develop anticancer drugs.

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