Browsing by Author "Santos, Tiago"
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- Enhanced Antimalarial Activity of Extracts of Artemisia annua L. Achieved with Aqueous Solutions of Salicylate Salts and Ionic LiquidsPublication . Ferreira, Ana M.; Sales, Isabela; Santos, Sónia A.O.; Santos, Tiago; Nogueira, Fátima; Mattedi, Silvana; Pinho, Simão; Coutinho, João A.P.; Freire, Mara G.Artemisinin, a drug used to treat malaria, can be chemically synthesized or extracted from Artemisia annua L. However, the extraction method for artemisinin from biomass needs to be more sustainable while maintaining or enhancing its bioactivity. This work investigates the use of aqueous solutions of salts and ionic liquids with hydrotropic properties as alternative solvents for artemisinin extraction from Artemisia annua L. Among the investigated solvents, aqueous solutions of cholinium salicylate and sodium salicylate were found to be the most promising. To optimize the extraction process, a response surface method was further applied, in which the extraction time, hydrotrope concentration, and temperature were optimized. The optimized conditions resulted in extraction yields of up to 6.50 and 6.44 mg·g-1, obtained with aqueous solutions of sodium salicylate and cholinium salicylate, respectively. The extracts obtained were tested for their antimalarial activity, showing a higher efficacy against the Plasmodium falciparum strain compared with pure (synthetic) artemisinin or extracts obtained with conventional organic solvents. Characterization of the extracts revealed the presence of artemisinin together with other compounds, such as artemitin, chrysosplenol D, arteannuin B, and arteannuin J. These compounds act synergistically with artemisinin and enhance the antimalarial activity of the obtained extracts. Given the growing concern about artemisinin resistance, the results here obtained pave the way for the development of sustainable and biobased antimalarial drugs. © 2024 The Authors. Co-published by Zhejiang University and American Chemical Society.
- A methanolic extract of Ganoderma lucidum fruiting body inhibits the growth of a gastric cancer cell line and affects cellular autophagy and cell cyclePublication . Oliveira, Beatriz; Reis, Filipa S.; Sousa, Diana; Tavares, Catarina; Lima, Raquel T.; Ferreira, Isabel C.F.R.; Santos, Tiago; Vasconcelos, M. HelenaGanoderma lucidum is one of the most extensively studied mushrooms as a functional food and as a chemopreventive agent due to its recognized medicinal properties. Some G. lucidum extracts have shown promising antitumor potential. In this study, the bioactive properties of various extracts of G. lucidum, from both the fruiting body and the spores, were investigated. The most potent extract identified was the methanolic fruiting body extract, which inhibited the growth of a gastric cancer cell line (AGS) by interfering with cellular autophagy and cell cycle.
- New di(hetero)aryl)ethers and Di(hetero)arylamines in the thieno[3,2-b]pyridine series: synthesis, growth inhibitory activity on tumor cell lines and non tumor cells, effects on cell cycle and on apoptosisPublication . Queiroz, Maria João R.P.; Peixoto, Daniela; Calhelha, Ricardo C.; Soares, Pedro; Santos, Tiago; Lima, Raquel T.; Campos, Joana F.; Abreu, Rui M.V.; Ferreira, Isabel C.F.R.; Vasconcelos, M. HelenaThe thienopyridine skeleton has been reported as having interesting biological activities namely antitumor[1,2] antiangiogenic.[3A] New fluorinated and methoxylated di(hetero)arylethers and di(hetero)arylamines were prepared functionalizing 7-position of the thieno[3,2-bJpyridine, using copper (C-O) or palladium (C-N) catalyzed couplings, respectively, of the 7-t>rolmo: thieno[3,2-bJpyridine (1) with ortho, meta and para fluoro or methoxy phenols and anilines.
- New di(hetero)arylethers and di(hetero)arylamines in the thieno[3,2-b]pyridine series: Synthesis, growth inhibitory activity on human tumor cell lines and non-tumor cells, effects on cell cycle and on programmed cell deathPublication . Queiroz, Maria João R.P.; Peixoto, Daniela; Calhelha, Ricardo C.; Soares, Pedro; Santos, Tiago; Lima, Raquel T.; Campos, Joana F.; Abreu, Rui M.V.; Ferreira, Isabel C.F.R.; Vasconcelos, M. HelenaNew fluorinated and methoxylated di(hetero)arylethers and di(hetero)arylamines were prepared functionalizing the 7-position of the thieno[3,2-b]pyridine, using copper (C–O) or palladium (C–N) catalyzed couplings, respectively, of the 7-bromothieno[3,2-b]pyridine, also prepared, with ortho, meta and para fluoro or methoxy phenols and anilines. The compounds obtained were evaluated for their growth inhibitory activity on the human tumor cell lines MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), HCT15 (colon carcinoma), HepG2 (hepatocellular carcinoma) and HeLa (cervical carcinoma). The most active compounds, a di(hetero)arylether with a methoxy group in the meta position relative to the ether function and two di(hetero)arylamines with a methoxy group either in the ortho or in the meta position relative to the NH, were further tested at their GI50 concentrations on NCI-H460 cells causing pronounced alterations in the cell cycle profile and a strong and significant increase in the programmed death of these cells. The fluorinated and the other methoxylated compounds did not show important activity, presenting high GI50 values in all the cell lines tested. Furthermore, the hepatotoxicity of the compounds was assessed using porcine liver primary cells (PLP2), established by some of us. Results showed that one of the most active compounds was not toxic to the non-tumor cells at their GI50 concentrations showing to be the most promising as antitumoral.
- Suillus luteus methanolic extract causes growth arrest independent of p53 in a human colon tumour cell line.Publication . Santos, Tiago; Ferreira, Isabel C.F.R.; Tavares, Catarina; Calhelha, Ricardo C.; Vaz, Josiana A.; Almeida, Gabriela M.; Vasconcelos, M. HelenaMushrooms are macrofungi and a powerful source of compounds with antitumour activity.
- Suillus luteus methanolic extract inhibits cell growth and proliferation of a colon cancer cell linePublication . Santos, Tiago; Tavares, Catarina; Sousa, Diana; Vaz, Josiana A.; Calhelha, Ricardo C.; Martins, Anabela; Almeida, Gabriela M.; Ferreira, Isabel C.F.R.; Vasconcelos, M. HelenaSeveral edible mushrooms extracts are known to have tumour cell growth inhibitory potential. The objective of this work was to study this potential in extracts of Suillus luteus collected from the Northeast of Portugal. Various extracts were prepared and their effect on tumour cell growth was studied with the SRB assay in four human tumour cell lines: MCF-7 (breast), NCI-H460 (non-small cell lung cancer), AGS (gastric) and HCT-15 (colon). The methanolic extract of S. luteus was the most potent extract. This extract was slightly more potent in the HCT-15 cells (with mutant p53, GI50=17.8 ± 1.6 µg/mL) than in the other cell lines tested, which suggested that its effect was not p53-dependent. Indeed, in HCT-15 cells, an increase in the levels of p53 was detected but no alterations in some of the proteins transactivated by p53 (e.g. p21 or Bax) were found. The extract caused an increase in the cellular levels of p-H2A.X, which is suggestive of DNA damage. Growth inhibition in these cells was mostly due to inhibition of cell proliferation and an increase in the % of cell in the G1 phase of the cell cycle. An increase in cell death was also found, even though to very low levels. In addition, this extract was not cytotoxic to primary cultures of porcine hepatocytes (GI50>400 µg/mL). Together, these results indicate that the S. luteus methanolic extract may be an interesting source of compounds that inhibit the proliferation of tumour cells but further studies should be carried out in order to understand its potential.
- Suillus luteus methanolic extract inhibits proliferation and increases expression of p-H2A.X in a non-small cell lung cancer cell linePublication . Santos, Tiago; Oliveira, Beatriz; Sousa, Diana; Lima, Raquel T.; Martins, Anabela; Ferreira, Isabel C.F.R.; Vasconcelos, M. HelenaMethanolic extract of Suillus luteus was previously shown to inhibit proliferation of colon cancer cells with mutant p53. The effect of the same extract was further investigated here in a wildtype (wt) p53 non-small cell lung cancer cell line. Treatment with the extract increased the levels of p-H2A.X and the number of p-H2A.X foci/cell, indicating a possible increase in deoxyribonucleic acid (DNA) damage. Nevertheless, it did not cause alterations in wt p53 levels nor in programmed cell death. The extract caused inhibition of cellular proliferation and an increase in the % of cells in the G0/G1 phase of the cell cycle. In conclusion, even though there is evidence of DNA damage being caused by this extract, there is no induction of cell death in this p53 wt cell line
- Tumour cell growth inhibitory potential of mushroom extracts from the genus SuillusPublication . Vaz, Josiana A.; Santos, Tiago; Tavares, Catarina; Calhelha, Ricardo C.; Martins, Anabela; Almeida, Gabriela M.; Ferreira, Isabel C.F.R.; Vasconcelos, M. HelenaMushrooms are a source of compounds with promising antitumour activity [1]. We have been working on the identification of wild mushrooms with promising antitumour activity and a Clitocybe alexandri extract which induces cell cycle arrest and apoptosis in a lung cancer cell line has been previously identified by part of the team [2]. The objective of this work was to continue the identification of mushrooms from the Northeast of Portugal with tumour cell growth inhibitory potential. Thirty six wild edible mushrooms were collected and taxonomically identified. Various extracts were prepared and screened for growth inhibitory potential with the SRB assay, in four human tumour cell lines: MCF-7 (breast), NCI-H460 (NSCLC), AGS (gastric) and HCT-15 (colon). These screens allowed the identification of two Suillus species whose methanolic extracts presented potent activity: S. collinitus and S. luteus. The S. collinitus extract was more potent in the MCF-7 cells (GI50=25.2±0.16 µg/ml), causing G1 cell cycle arrest and increasing apoptosis. An increase in p53 and p21 was verified, suggesting that the effect was p53-mediated [3]. The S. luteus extract was slightly more potent in the HCT-15 cells (with mutant p53, GI50=17.8 ± 1.6 µg/ml) than in the other cell lines tested, indicating that its effect was not p53-dependent. In fact, it increased the levels of p53 but the alterations in proteins transactivated by p53 (e.g. Bax) were not consistent with a p53-mediated effect. Growth inhibition in the HCT-15 cells was mostly due to inhibition of cell proliferation and cell cycle arrest in G1, rather than induction of cell death. Finally, this extract had no effect in primary cultures of porcine hepatocytes (GI50>400 µg/ml). In conclusion, these two Suillus species present promising tumour cell growth inhibitory effect and the S. luteus extract may be particularly interesting considering that most tumours present mutant p53.