Browsing by Author "Vasconcelos, M. Helena"
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- Achillea millefolium L. hydroethanolic extract inhibits growth of human tumor cell lines by interfering with cell cycle and inducing apoptosisPublication . Pereira, Joana M.; Peixoto, Vanessa; Teixeira, Alexandra Margarida; Sousa, Diana; Barros, Lillian; Ferreira, Isabel C.F.R.; Vasconcelos, M. Helena
- Aminodi(hetero)arylamines in the thieno[3,2-b]pyridine series: synthesis, effects in human tumor cells growth, cell cycle analysis, apoptosis and evaluation of toxicity using non-tumor cellsPublication . Calhelha, Ricardo C.; Ferreira, Isabel C.F.R.; Peixoto, Daniela; Abreu, Rui M.V.; Vale-Silva, Luís A.; Pinto, Eugénia; Lima, Raquel T.; Alvelos, M. Inês; Vasconcelos, M. Helena; Queiroz, Maria João R.P.Three aminodi(hetero)arylamines were prepared via a palladium-catalyzed C-N Buchwald-Hartwig coupling of methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate with different bromonitrobenzenes, followed by reduction of the nitro groups of the coupling products to the corresponding amino compounds. The aminodi(hetero)arylamines thus obtained were evaluated for their growth inhibitory effect on four human tumor cell lines MCF-7 (breast adenocarcinoma), A375-C5 (melanoma), NCI-H460 (non-small cell lung cancer) and HepG2 (hepatocellular carcinoma). The toxicity to non-tumor cells was also evaluated using a porcine liver primary cell culture (PLP1), established by us. The aminodi(hetero)arylamine with the NH2 group in the ortho position and an OMe group in the para position to the NH of the di(hetero)arylamine, is the most promising compound giving the lowest GI50 values (1.30–1.63 μM) in all the tested human tumor cell lines, presenting no toxicity to PLP1 at those concentrations. The effect of this compound on the cell cycle and induction of apoptosis was analyzed in the NCI-H460 cell line. It was observed that it altered the cell cycle profile causing a decrease in the percentage of cells in the G0/G1 phase and an increase of the apoptosis levels.
- An aqueous extract of tuberaria lignosa inhibits cell growth, alters the cell cycle profile, and induces apoptosis of NCI-H460 tumor cellsPublication . Pereira, Joana M.; Lopes-Rodrigues, Vanessa; Xavier, Cristina; Lima, M. João; Lima, Raquel T.; Ferreira, Isabel C.F.R.; Vasconcelos, M. HelenaTuberaria lignosa (Sweet) Samp. is found in European regions, and has antioxidant properties due to its composition in ascorbic acid and phenolic compounds. Given its traditional use and antioxidant properties, the tumor cell growth inhibitory potential of aqueous extracts from T. lignosa (prepared by infusion and decoction) was investigated in three human tumor cell lines: MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), and HCT-15 (human colorectal adenocarcinoma). Both extracts inhibited the growth of these cell lines; the most potent one being the T. lignosa extract obtained by infusion in the NCI-H460 cells (GI50 of approximately 50 μg/mL). Further assays were carried out with this extract in NCI-H460 cells. At 100 μg/mL or 150 μg/mL it caused an increase in the percentage of cells in the G0/G1 phase and a decrease of cells in S phase of the cell cycle. Additionally, these concentrations caused an increase in the percentage of apoptotic cells. In agreement, a decrease in total poly (ADP-ribose) polymerase (PARP) and pro-caspase 3 levels was found. In conclusion, the T. lignosa extract obtained by infusion was more potent in NCI-H460 cells, altering the cell cycle progression and inducing apoptosis. This work highlights the importance of T. lignosa as a source of bioactive compounds with tumor cell growth inhibitory potential.
- Anti-hepatocellular carcinoma activity using human HepG2 cells and hepatotoxicity of 6-substituted methyl 3-aminothieno[3,2-b]pyridine-2- carboxylate derivatives: In vitro evaluation, cell cycle analysis and QSAR studiesPublication . Abreu, Rui M.V.; Ferreira, Isabel C.F.R.; Calhelha, Ricardo C.; Lima, Raquel T.; Vasconcelos, M. Helena; Adega, Filomena; Chaves, Raquel; Queiroz, Maria João R.P.Hepatocellular carcinoma (HCC) is a highly complex cancer, resistant to commonly used treatments and new therapeutic agents are urgently needed. A total of thirty-two thieno[3,2-b]pyridine derivatives of two series: methyl 3-amino- -(hetero)arylthieno[3,2-b]pyridine-2-carboxylates (1ae1t) and methyl 3-amino-6-[(hetero)arylethynyl]thieno[3,2-b]pyridine-2-carboxylates (2ae2n), previously prepared by some of us, were evaluated as new potential anti-HCC agents by studying their in vitro cell growth inhibition on human HepG2 cells and hepatotoxicity using a porcine liver primary cell culture (PLP1). The presence of amino groups linked to a benzene moiety emerges as the key element for the anti-HCC activity. The methyl 3-amino-6-[(3-aminophenyl)ethynyl]thieno[3,2-b]pyridine-2-carboxylate (2f) is the most potent compound presenting GI50 values on HepG2 cells of 1.2 mM compared to 2.9 mM of the positive control ellipticine, with no observed hepatotoxicity (PLP1 GI50 > 125 mM against 3.3 mM of ellipticine). Moreover this compound changes the cell cycle profile of the HepG2 cells, causing a decrease in the % of cells in the S phase and a cell cycle arrest in the G2/M phase. QSAR studies were also performed and the correlations obtained using molecular and 1D descriptors revealed the importance of the presence of amino groups and hydrogen bond donors for anti-HCC activity, and hydrogen bond acceptors for hepatotoxicity. The best correlations were obtained with 3D descriptors belonging to different subcategories for anti-HCC activity and hepatotoxicity, respectively. These results point to different molecular mechanisms of action of the compounds in anti-HCC activity and hepatotoxicity. This work presents some promising thieno[3,2-b]pyridine derivatives for potential use in the therapy of HCC. These compounds can also be used as scaffolds for further synthesis of more potent analogs.
- Antioxidant activity and growth inhibitory activity of Portuguese wild mushroomsPublication . Vaz, Josiana A.; Heleno, Sandrina A.; Martins, Anabela; Almeida, Gabriela M.; Vasconcelos, M. Helena; Ferreira, Isabel C.F.R.Some mushrooms are a powerful source of bioactive compounds including antioxidants, inhibitors of human tumour cell lines growth, inducers of apoptosis and ent1ancers of immunity. Indeed, many pre-clinical studies have been conducted in human tumour cell lines and in some cases a number of compounds extracted from mushrooms have followed to Pl1ases I , l l and Ill of clinical trials. There is an enormous source of wild mushrooms in Portugal, particularly in the North. However, to our knowledge, no studies have been conducted so far to verify their bioactivities.
- Antioxidant activity and growth inhibitory activity of Portuguese wild mushroomsPublication . Vaz, Josiana A.; Martins, Anabela; Almeida, Gabriela M.; Vasconcelos, M. Helena; Ferreira, Isabel C.F.R.
- Avaliação da bioatividade do corpo frutífero e esporos de Ganoderma lucidumPublication . Heleno, Sandrina A.; Tavares, Catarina; Vaz, Josiana A.; Almeida, Gabriela M.; Vasconcelos, M. Helena; Martins, Anabela; Queiroz, Maria João R.P.; Ferreira, Isabel C.F.R.Ganoderma lucidum (Curtis) P. Karst. é uma das espécies de cogumelos mais estudadas do mundo devido às suas propriedades medicinais [1]. Este trabalho descreve a avaliação da capacidade antioxidante in vitro e antiproliferativa em células tumorais do extrato obtido a partir de diferentes partes do cogumelo. Os exemplares de Ganoderma lucidum foram colhidos em Bragança e divididos em duas amostras: corpo frutífero e esporos. A atividade antioxidante dos extratos metanólicos, obtidos a partir das duas amostras, foi avaliada através da captação de radicais livres, poder redutor e inibição da peroxidação lipídica pela descoloração do β-caroteno e em homogeneizados de células cerebrais animais. A atividade antiproliferativa dos mesmos extratos foi avaliada em quatro linhas celulares tumorais humanas (pulmão- NCI-H460, mama- MCF-7, cólon- HCT-15 e estômago- AGS) pelo método da sulforrodamina B. O extrato obtido a partir do corpo frutífero revelou maior atividade antioxidante (EC50 entre 0,10 e 0,62 mg/mL) do que o extrato de esporos (EC50 entre 0,58 e 1,61 mg/mL). O extrato obtido a partir do corpo frutífero revelou uma atividade antiproliferativa em linhas celulares tumorais moderada (GI50 entre 93,3 e 112,6 μg/mL), enquanto o extrato obtido a partir dos esporos mostrou uma baixa atividade nas linhas celulares NCI-H460 e HCT15 e nenhuma atividade nas restantes linhas na máxima concentração testada (400 μg/mL). Os extratos foram caracterizados por HPLC-DAD-MS [2]. O corpo frutífero apresentou maior quantidade de ácidos fenólicos (1,23 mg/100 g massa seca) do que os esporos (0,61 mg/100g massa seca). Os ácidos p-hidroxibenzóico (0,58 mg/100 g) e p-cumárico (0.38 mg/100 g) foram os principais ácidos fenólicos identificados no corpo frutífero, bem como o ácido cinâmico (0,28 mg/100 g). Os esporos não apresentaram ácido p-hidroxibenzóico. Apesar dos compostos fenólicos estarem associados a vários efeitos benéficos para a saúde humana, pouco se sabe sobre as formas bioativas in vivo, atendendo às concentrações disponíveis na corrente sanguínea após ingestão, assim como à possibilidade de conjugação e metabolismo. Estão a sintetizar-se possíveis metabolitos dos compostos identificados nos extratos para avaliar a sua potencial bioatividade.
- Avaliação da bioatividade do corpo frutífero e esporos de Ganoderma lucidumPublication . Heleno, Sandrina A.; Tavares, Catarina; Vaz, Josiana A.; Almeida, Gabriela M.; Vasconcelos, M. Helena; Martins, Anabela; Queiroz, Maria João R.P.; Ferreira, Isabel C.F.R.Ganoderma lucidum é uma das espécies de cogumelos mais estudadas do mundo devido às suas propriedades medicinais. Este trabalho descreve a avaliação da capacidade antioxidante in vitro e antiproliferativa em células tumorais do extrato obtido a partir de diferentes partes do cogumelo. A atividade antioxidante dos extratos metanólicos, obtidos a partir das duas amostras, foi avaliada através da captação de radicais livres, poder redutor e inibição da peroxidação lipídica pela descoloração do β-caroteno e em homogeneizados de células cerebrais animais. A atividade antiproliferativa dos mesmos extratos foi avaliada em quatro linhas celulares tumorais humanas (pulmão- NCI-H460, mama- MCF-7, cólon- HCT-15 e estômago- AGS) pelo método da sulforrodamina B. Os extratos foram caracterizados por HPLC-DAD-MS.
- Bioactive properties of Clitocybe alexandriPublication . Vaz, Josiana A.; Heleno, Sandrina A.; Martins, Anabela; Almeida, Gabriela M.; Vasconcelos, M. Helena; Ferreira, Isabel C.F.R.Some mushrooms may have antioxidant and tumour cell growth inhibitory activities. However, there is no data on Portuguese wild mushrooms. The aim of this work was lo study extracts obtained from the Portuguese wild mushroom Clitocybe alexandri, regard the in vitro antioxidant acclivity and the growth inhibitory activity in human tumour cell lines.
- Bioactive properties of Clitocybe alexandriPublication . Vaz, Josiana A.; Heleno, Sandrina A.; Martins, Anabela; Almeida, Gabriela M.; Vasconcelos, M. Helena; Ferreira, Isabel C.F.R.Some mushrooms are known to have strong antioxidant capacity [1]. There is an accepted relationship between the physiopathology of several chronic diseases and oxidative stress. Therefore, the use of foods such as those mushrooms with antioxidant capacity, as phytochemical protectors, may be relevant for the prevention of oxidative stress related diseases such as cancer. Additionally, mushrooms have been described as a source of potential antitumour molecules, making them attractive candidates for drug discovery [2,3]. However, there are no such studies on the Portuguese wild mushroom Clitocybe alexandri .