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Maria Emília Sousa   Professor  University Educator/Researcher 
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Maria Emília Sousa published an article in January 2019.
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Top co-authors See all
Paula B. Andrade

306 shared publications

REQUIMTE/LAQV, Laboratory of Pharmacognosy, Departament of Chemistry, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira, no. 228, 4050-313 Porto, Portugal

Victor De Freitas

229 shared publications

REQUIMTE/LAQV, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, Portugal

F. Javier Luque

206 shared publications

Department of Nutrition, Food Sciences and Gastronomy, Faculty of Pharmacy and Food Sciences, Institute of Biomedicine (IBUB) and Institute of Theoretical and Computational Chemistry (IQTC), University of Barcelona, Av. Prat de la Riba 171, E-08921 Santa Coloma de Gramenet, Spain

Madalena Pinto

205 shared publications

Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal

Maria De Lourdes Bastos

196 shared publications

University of Porto

67
Publications
191
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55
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217
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Publication Record
Distribution of Articles published per year 
(2002 - 2019)
Total number of journals
published in
 
27
 
Publications See all
Article 0 Reads 0 Citations Chemistry of the fumiquinazolines and structurally related alkaloids Diana I. S. P. Resende, Papichaya Boonpothong, Emília Sousa,... Published: 01 January 2019
Natural Product Reports, doi: 10.1039/c8np00043c
DOI See at publisher website
EDITORIAL 0 Reads 0 Citations Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes–4 Arduino A Mangoni, Catherine Guillou, Jean Jacques Vanden Ey... Published: 31 December 2018
Molecules, doi: 10.3390/molecules24010130
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Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes is a series of Editorials, which is published on a biannual basis by the Editorial Board of the Medicinal Chemistry section of the journal Molecules.
Article 1 Read 0 Citations The Antitumor Activity of a Lead Thioxanthone is Associated with Alterations in Cholesterol Localization Raquel T. Lima, Diana Sousa, Ana Sara Gomes, Nuno Mendes, Ru... Published: 12 December 2018
Molecules, doi: 10.3390/molecules23123301
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The search for novel anticancer small molecules and strategies remains a challenge. Our previous studies have identified TXA1 (1-{[2-(diethylamino)ethyl]amino}-4-propoxy-9H- thioxanthen-9-one) as a hit compound, with in vitro antitumor potential by modulating autophagy and apoptosis in human tumor cell lines. In the present study, the mechanism of action and antitumor potential of the soluble salt of this molecule (TXA1.HCl) was further investigated using in vitro and mouse xenograft tumor models of NSCLC. Our results showed that TXA1.HCl affected steroid biosynthesis, increased RagD expression, and caused abnormal cellular cholesterol localization. In addition, TXA1.HCl treatment presented no toxicity to nude mice and significantly reduced the growth of human NSCLC cells xenografts in mice. Overall, this work provides new insights into the mechanism of action of TXA1, which may be relevant for the development of anticancer therapeutic strategies, which target cholesterol transport.
Article 1 Read 0 Citations Lichen Xanthones as Models for New Antifungal Agents Diana I. S. P. Resende, Patrícia Pereira-Terra, Ângela S. In... Published: 12 October 2018
Molecules, doi: 10.3390/molecules23102617
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Due to the emergence of multidrug-resistant pathogenic microorganisms, the search for new antimicrobial compounds plays an important role in current medicinal chemistry research. Inspired by lichen antimicrobial xanthones, a series of novel chlorinated xanthones was prepared using five chlorination methods (Methods A–E) to obtain different patterns of substitution in the xanthone scaffold. All the synthesized compounds were evaluated for their antimicrobial activity. Among them, 3-chloro-4,6-dimethoxy-1-methyl-9H-xanthen-9-one 15 showed promising antibacterial activity against E. faecalis (ATCC 29212 and 29213) and S. aureus ATCC 29213. 2,7-Dichloro-3,4,6-trimethoxy-1-methyl-9H-xanthen-9-one 18 revealed a potent fungistatic and fungicidal activity against dermatophytes clinical strains (T. rubrum, M. canis, and E. floccosum (MIC = 4–8 µg/mL)). Moreover, when evaluated for its synergistic effect for T. rubrum, compound 18 exhibited synergy with fluconazole (ΣFIC = 0.289). These results disclosed new hit xanthones for both antibacterial and antifungal activity.
Article 0 Reads 0 Citations Old Drugs as New Treatments for Neurodegenerative Diseases. Fernando Durães, Madalena Pinto, Emília Sousa Published: 11 May 2018
Pharmaceuticals,
PubMed View at PubMed ABS Show/hide abstract
Neurodegenerative diseases are increasing in number, given that the general global population is becoming older. They manifest themselves through mechanisms that are not fully understood, in many cases, and impair memory, cognition and movement. Currently, no neurodegenerative disease is curable, and the treatments available only manage the symptoms or halt the progression of the disease. Therefore, there is an urgent need for new treatments for this kind of disease, since the World Health Organization has predicted that neurodegenerative diseases affecting motor function will become the second-most prevalent cause of death in the next 20 years. New therapies can come from three main sources: synthesis, natural products, and existing drugs. This last source is known as drug repurposing, which is the most advantageous, since the drug’s pharmacokinetic and pharmacodynamic profiles are already established, and the investment put into this strategy is not as significant as for the classic development of new drugs. There have been several studies on the potential of old drugs for the most relevant neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Multiple Sclerosis and Amyotrophic Lateral Sclerosis.
CONFERENCE-ARTICLE 9 Reads 0 Citations <strong>Synthesis and Tumor Cell Growth Inhibitory Effects of New Flavonosides and Xanthonosides</strong> Ana Rita Neves, Marta Correia-da-Silva, Patrícia M.A. Silva,... Published: 01 November 2017
3rd International Electronic Conference on Medicinal Chemistry, doi: 10.3390/ecmc-3-04688
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Natural flavonoid and xanthone glycosides display several biological activities [1-3], with the glycoside moiety playing an important role in the mechanisms of action of these metabolites. Herein, to give further insights into the inhibitory cell growth activity of these classes of compounds, the synthesis of new flavonoid and xanthone derivatives containing one or more acetoglycoside moieties was carried out to evaluate their in vitro cell growth inhibitory activity in human tumor cell lines.

The introduction of one or two acetoglycoside moieties in the skeleton of a hydroxylated flavonoid was performed using three synthetic methods: Michael reaction, Koenigs-Knorr reaction, and through a copper-catalyzed azide-alkyne cycloaddition. Acetyl groups were introduced in rutin, diosmin, and mangiferin using acetic anhydride under microwave irradiation. The in vitro cell growth inhibitory activity of seven synthesized compounds was investigated in six human tumor cell lines: A375- C5 (malignant melanoma IL-1 insensitive), MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), U251 (glioblastoma astrocytoma), U373 (glioblastoma astrocytoma), and U87MG (glioblastoma astrocytoma). The most active compound in all tumor cell lines tested was a flavonoside and showed GI50 values below 10 μM.

[1] Leong, C.N.A., et al., Food Chemistry, 2008. 109(2): p. 415-420.

[2] Kumar, M., et al., Fitoterapia, 2010. 81(4): p. 234-242.

[3] Reutrakul, V., et al., Planta Medica, 2007. 73(7): p. 683-688.

 

Acknowledgments:

The authors want to thank Fundação da Ciência e Tecnologia (FCT/MCTES, PIDDAC) and European Regional Development Fund (ERDF) for funding this research through the COMPETE – Programa Operacional Factores de Competitividade (POFC) programme (POCI-01-0145‐FEDER-016790 and POCI-01-0145-FEDER-016793), Reforçar a Investigação, o Desenvolvimento Tecnológico e a Inovação (RIDTI, Project 3599 and 9471), and INNOVMAR, reference NORTE-01-0145-FEDER-000035, Research Line NOVELMAR, under the projects PTDC/ MAR-BIO/4694/2014 and PTDC/AAG-TEC/0739/2014 and the Strategic Funding UID/Multi/04423/2013 through national funds provided by FCT and ERDF, in the framework of the programme PT2020. Ana R. Neves wants to thank FCT for the Ph.D. fellowship (SFRH/BD/114856/2016).

Conference papers
CONFERENCE-ARTICLE 39 Reads 0 Citations Small molecules from the sea: models for innovative antimicrobial agents Solida Long, Diana Resende, Patrícia Pereira-Terra, Ângela I... Published: 31 October 2018
doi: 10.3390/ecmc-4-05597
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Antimicrobial resistance is one of the most pressing health issues of our days. The marine environment has proven to be a very rich source of diverse natural products with broad-spectra of biologically activities being a very helpful resource in the search for novel antimicrobial compounds. These structurally distinct molecules are revealing promising biological activities against a very large number of drug-resistant pathogenic bacteria and fungi, catching marine natural products attention in the discovery of new antimicrobial agents. Inspired by antimicrobial lichen xanthones [1] and fungi-derived alkaloids, two series of marine natural products mimics were prepared. The synthesized compounds were evaluated for their antimicrobial activity. Both series produced interesting compounds active against E. faecalis (ATCC 29212 and 29213) and S. aureus (ATCC 29213) with some synthetic alkaloids being active against a MRSA strain. Some revealed a potent fungistatic and fungicidal activity against dermatophytes clinical strains (T. rubrum, M. canis, and E. floccosum). These results highlight the potential of marine natural products as a source of new antimicrobial agents to revert resistance.

[1] D. I. S. P. Resende, P. Pereira-Terra, Â. S. Inácio, P. M. Costa, E. Pinto, E. Sousa, M. M. M. Pinto. Lichen Xanthones as Models for New Antifungal Agents. Molecules 2018, 23, 2617; doi:10.3390/molecules23102617

Acknowledgments: This work was partially supported through national funds provided by FCT/MCTES—Foundation for Science and Technology from the Ministry of Science, Technology, and Higher Education (PIDDAC) and the European Regional Development Fund (ERDF) through the COMPETE—Programa Operacional Factores de Competitividade (POFC) programme, under the Strategic Funding UID/Multi/04423/2013, the projects POCI-01-0145-FEDER-028736 and POCI-01-0145-FEDER-016790 (PTDC/MAR-BIO/4694/2014; 3599-PPCDT) in the framework of the programme PT2020, as well as by the project INNOVMAR—Innovation and Sustainability in the Management and Exploitation of Marine Resources (reference NORTE-01-0145-FEDER-000035, within Research Line NOVELMAR), supported by North Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). Solida Long thanks Erasmus Mundus Action 2 (LOTUS+, LP15DF0205) for full PhD scholarship. Diana I. S. P. Resende also acknowledge for her grant (NOVELMAR/BPD_2/2016-019) and Patrícia Pereira-Terra for her grant (NOVELMAR/BPD/2017/012).

CONFERENCE-ARTICLE 14 Reads 0 Citations <em>In silico </em>studies of aminated thioxanthones: bacterial multidrug efflux pumps <em>vs</em> P-glycoprotein Fernando Durães, Andreia Palmeira, Madalena Pinto, Emília So... Published: 31 October 2018
doi: 10.3390/ecmc-4-05598
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Currently, one of the most urgent threats is antimicrobial resistance, which leads to the inefficacy of drugs in therapeutics, and can arise from several reasons, being the overexpression of efflux pumps one of them. These pumps are ubiquitous in bacteria, and their overexpression allows bacteria to develop multidrug resistance, through the extrusion of antimicrobial drugs. They can be divided into five families, being the resistance-nodulation-division (RND) family and the major facilitator superfamily (MFS) the most relevant. Efforts have been put towards a selective, efficient efflux pump inhibitor (EPI), and although some progress has been achieved, in the therapeutic scenario no EPIs have been approved.1

Our group has experience in molecular docking and synthesis of aminated thioxanthones with modulatory activity in the mammal efflux pump P-glycoprotein (P-gp), which is also useful in the detoxification of xenobiotics.2,3 Taking this into account, the aim of this work was the design of a virtual library of approximately 1.000 aminated (thio)xanthones, the performance of docking studies in bacterial efflux pumps whose crystal structure has been elucidated and available in the Protein Data Bank and in a model of the human P-gp. For the docking studies bacterial efflux pumps chosen were both from the RND family: AcrB, from the AcrAB-TolC efflux system,4 and MexB, from the MexAB-OprM efflux system.5

The compounds that will be selected for synthesis are the ones that virtually displayed good scores for the bacterial referred efflux pumps and lower scores for P-gp, since this would mean that, in vivo, these compounds would efficiently reduce antimicrobial resistance while not interfering with human detoxification pathways.

Acknowledgements: This research was developed under Project No. POCI-01-0145-FEDER-028736, co-financed by COMPETE 2020, Portugal 2020 and the European Union through the ERDF, and by FCT through national funds.

References:

  1. Durães, F.; Pinto, M.; Sousa, E., Medicinal Chemistry Updates on Bacterial Efflux Pump Modulators. Curr Med Chem 2018, Feb 9. doi: 10.2174/0929867325666180209142612.
  2. Palmeira, A.; Vasconcelos, M. H.; Paiva, A.; Fernandes, M. X.; Pinto, M.; Sousa, E., Dual inhibitors of P-glycoprotein and tumor cell growth: (re)discovering thioxanthones. Biochem Pharmacol 2012, 83 (1), 57-68.
  3. Palmeira, A.; Rodrigues, F.; Sousa, E.; Pinto, M.; Vasconcelos, M. H.; Fernandes, M. X., New uses for old drugs: pharmacophore-based screening for the discovery of P-glycoprotein inhibitors. Chem Biol Drug Des 2011, 78 (1), 57-72.
  4. Yu, E. W.; Aires, J. R.; McDermott, G.; Nikaido, H., A periplasmic drug-binding site of the AcrB multidrug efflux pump: a crystallographic and site-directed mutagenesis study. J Bacteriol 2005, 187 (19), 6804-15.
  5. Sennhauser, G.; Bukowska, M. A.; Briand, C.; Grutter, M. G., Crystal structure of the multidrug exporter MexB from Pseudomonas aeruginosa. Journal of molecular biology 2009, 389 (1), 134-45.
CONFERENCE-ARTICLE 26 Reads 0 Citations <span>Biologically-active sulfated steroids: synthesis and state-of-art </span> Francisca Carvalhal, Ana Neves, Amadeu Câmara, Emília Sousa,... Published: 31 October 2018
doi: 10.3390/ecmc-4-05574
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Several biological activities from nearly 150 marine-derived sulfated steroids have been reported with both pharmacological (antimicrobial, antitumor, cardiovascular and/ or anti-inflammatory activities) and environmental (antifouling activity) applications [1]. Sulfation is used in Nature to avoid toxicity and therefore marine-inspired sulfated steroids could be an interesting strategy for drug discovery. The sulfated aminosterol squalamine, isolated from the internal organs of the dogfish shark, is in phase III of clinical trials as anti-angiogenic drug [2], which evidences the potential of sulfated steroids.

Sulfation of small molecules using sulfur trioxide-amine complexes entails several advantages, such as persulfation, low degradation, and feasibility in the work-up [3]. Moreover, these complexes appear to be suitable for sulfation of alcohol groups present in steroids [4]. In this direction, sulfation of four sterols was achieved using triethylamine-sulfur trioxide adduct in dimethylacetamide under heating, with yields ranging from 3% to 93%. Purification involved insolubilization with diethyl ether followed by several methods to obtain the sulfated derivatives free of inorganic impurities, including dialysis and/ or chromatographic processes. Structure elucidation of these new compounds was established by infrared (IR), nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HRMS). Biological activities will be further studied.

Acknowledgements:

This work was supported through national funds provided by FCT/MCTES - Foundation for Science and Technology from the Ministry of Science, Technology and Higher Education (PIDDAC) and European Regional Development Fund (ERDF) through the COMPETE Programa Operacional Factores de Competitividade (POFC) programme, under the projects PTDC/MAR-BIO/4694/2014 (reference POCI-01-0145-FEDER-016790; Project 3599–PPCDT), PTDC/AAGTEC/0739/2014 (reference POCI-01-0145-FEDER-016793; Project 9471-RIDTI) and POCI-01-0145-FEDER-028736 in the framework of the programme PT2020. Carvalhal F also acknowledges FCT for the grant PTDC/AAG- TEC/0739/2014-018.

References:

[1] Carvalhal, F., M. Correia-da-Silva, M.E. Sousa, M. Pinto, and A. Kijjoa, Journal of Molecular Endocrinology, 2018, 61(2) 211-231.

[2] NCT02727881 (https://clinicaltrials.gov/ct2/show/NCT02727881, October 15, 2018)

[3] Correia-da-Silva, M., E. Sousa, and M.M. Pinto, Medicinal Research Reviews, 2014, 34(2) 223-79.

[4] Al-Horani, R.A., and U.R. Desai, Chemical Sulfation of Small Molecules - Advances and Challenges.Tetrahedron, 2010, 66(16), 2907-2918

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