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Madalena Pinto   Professor  Senior Scientist or Principal Investigator 
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Madalena Pinto published an article in January 2019.
Top co-authors See all
Artur M.S. Silva

518 shared publications

Department of chemistry and QOPNA; University of Aveiro; Campus of Santiago Aveiro Portugal

Maria De Lourdes Bastos

196 shared publications

University of Porto

Anake Kijjoa

106 shared publications

ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal

Fernando Remiao

97 shared publications

UCIBIO-REQUIMTE, Laboratório de Toxicologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal

Maria João Rocha

84 shared publications

ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal

195
Publications
304
Reads
84
Downloads
217
Citations
Publication Record
Distribution of Articles published per year 
(1974 - 2019)
Total number of journals
published in
 
33
 
Publications See all
Article 0 Reads 0 Citations Chiral Derivatives of Xanthones with Antimicrobial Activity Joana Araújo, Carla Fernandes, Madalena Pinto, Maria Elizabe... Published: 16 January 2019
Molecules, doi: 10.3390/molecules24020314
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According to the World Health Organization, the exacerbated use of antibiotics worldwide is increasing multi-resistant infections, especially in the last decade. Xanthones are a class of compounds receiving great interest in drug discovery and development that can be found as natural products or obtained by synthesis. Many derivatives of xanthones are chiral and associated with relevant biological activities, including antimicrobial. The aim of this review is to compile information about chiral derivatives of xanthones from natural sources and their synthesized examples with antimicrobial activity.
Article 0 Reads 0 Citations Structures, Activities and Drug-Likeness of Anti-Infective Xanthone Derivatives Isolated from the Marine Environment: A ... Daniela R. P. Loureiro, José X. Soares, Joana C. Costa, Álv... Published: 10 January 2019
Molecules, doi: 10.3390/molecules24020243
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Marine organisms represent almost half of total biodiversity and are a very important source of new bioactive substances. Within the varied biological activities found in marine products, their antimicrobial activity is one of the most relevant. Infectious diseases are responsible for high levels of morbidity and mortality and many antimicrobials lose their effectiveness with time due to the development of resistance. These facts justify the high importance of finding new, effective and safe anti-infective agents. Among the variety of biological activities of marine xanthone derivatives, one that must be highlighted is their anti-infective properties. In this work, a literature review of marine xanthones with anti-infective activity, namely antibacterial, antifungal, antiparasitic and antiviral, is presented. Their structures, biological activity, sources and the methods used for bioactivity evaluation are described. The xanthone derivatives are grouped in three sets: xanthones, hydroxanthones and glycosylated derivatives. Moreover, molecular descriptors, biophysico-chemical properties, and pharmacokinetic parameters were calculated, and the chemical space occupied by marine xanthone derivatives is recognized. The chemical space was compared with marketed drugs and framed accordingly to the drug-likeness concept in order to profile the pharmacokinetic of anti-infective marine xanthone derivatives.
Article 0 Reads 0 Citations Erubescensoic Acid, a New Polyketide and a Xanthonopyrone SPF-3059-26 from the Culture of the Marine Sponge-Associated F... Decha Kumla, Tida Dethoup, Luís Gales, José A. Pereira, Joan... Published: 08 January 2019
Molecules, doi: 10.3390/molecules24010208
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A new polyketide erubescensoic acid (1), and the previously reported xanthonopyrone, SPF-3059-26 (2), were isolated from the uninvestigated fractions of the ethyl acetate crude extract of the marine sponge-associated fungus Penicillium erubescens KUFA0220. The structures of the new compound, erubescensoic acid (1), and the previously reported SPF-3059-26 (2), were elucidated by extensive analysis of 1D and 2D-NMR spectra as well as HRMS. The absolute configuration of the stereogenic carbon of erubescensoic acid (1) was determined by X-ray analysis. Erubescensoic acid (1) and SPF-3059-26 (2), together with erubescenschromone B (3), penialidin D (4), and 7-hydroxy-6-methoxy-4-oxo-3-[(1E)-3-oxobut-1-en-1-yl]-4H-chromen-5-carboxylic acid (5), recently isolated from this fungus, were assayed for their antibacterial activity against gram-positive and gram-negative reference strains and the multidrug-resistant (MDR) strains from the environment. The capacity of these compounds to interfere with the bacterial biofilm formation and their potential synergism with clinically relevant antibiotics for the MDR strains were also investigated.
Article 0 Reads 0 Citations Carboxyxanthones: Bioactive Agents and Molecular Scaffold for Synthesis of Analogues and Derivatives João Ribeiro, Cláudia Veloso, Carla Fernandes, Maria Elizabe... Published: 05 January 2019
Molecules, doi: 10.3390/molecules24010180
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Xanthones represent a structurally diverse group of compounds with a broad range of biological and pharmacological activities, depending on the nature and position of various substituents in the dibenzo-γ-pyrone scaffold. Among the large number of natural and synthetic xanthone derivatives, carboxyxanthones are very interesting bioactive compounds as well as important chemical substrates for molecular modifications to obtain new derivatives. A remarkable example is 5,6-dimethylxanthone-4-acetic acid (DMXAA), a simple carboxyxanthone derivative, originally developed as an anti-tumor agent and the first of its class to enter phase III clinical trials. From DMXAA new bioactive analogues and derivatives were also described. In this review, a literature survey covering the report on carboxyxanthone derivatives is presented, emphasizing their biological activities as well as their application as suitable building blocks to obtain new bioactive derivatives. The data assembled in this review intends to highlight the therapeutic potential of carboxyxanthone derivatives and guide the design for new bioactive xanthone derivatives.
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
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Article 0 Reads 0 Citations New Alkoxy Flavone Derivatives Targeting Caspases: Synthesis and Antitumor Activity Evaluation Joana Moreira, Diana Ribeiro, Patrícia M. A. Silva, Nair Naz... Published: 31 December 2018
Molecules, doi: 10.3390/molecules24010129
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The antitumor activity of natural flavonoids has been exhaustively reported. Previously it has been demonstrated that prenylation of flavonoids allows the discovery of new compounds with improved antitumor activity through the activation of caspase-7 activity. The synthesis of twenty-five flavonoids (4–28) with one or more alkyl side chains was carried out. The synthetic approach was based on the reaction with alkyl halide in alkaline medium by microwave (MW) irradiation. The in vitro cell growth inhibitory activity of synthesized compounds was investigated in three human tumor cell lines. Among the tested compounds, derivatives 6, 7, 9, 11, 13, 15, 17, and 18 revealed potent growth inhibitory activity (GI50 < 10 μM), being the growth inhibitory effect of compound 13 related with a pronounced caspase-7 activation on MCF-7 breast cancer cells and yeasts expressing human caspase-7. A quantitative structure-activity relationship (QSAR) model predicted that hydrophilicity, pattern of ring substitution/shape, and presence of partial negative charged atoms were the descriptors implied in the growth inhibitory effect of synthesized compounds. Docking studies on procaspase-7 allowed predicting the binding of compound 13 to the allosteric site of procaspase-7.
Conference papers See all
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 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

CONFERENCE-ARTICLE 29 Reads 0 Citations Dual application of chiral derivatives of xanthones in medicinal chemistry and liquid chromatography Carla Fernandes, Ye Phyo, João Ribeiro, Sara Cravo, Maria Ti... Published: 31 October 2018
doi: 10.3390/ecmc-4-05604
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Over several years, xanthone derivatives have been the core of several studies, essentially due their wide range of biological and pharmacological activities [1]. Recently, chiral derivatives of xanthones (CDXs) have come to arouse great interest considering enantioselectivity studies associated with biological activities [2,3] as well as selectors for chiral stationary phases (CSPs) in liquid chromatography (LC) [4,5].

From the perspective of Medicinal Chemistry, some CDXs synthetized by our group revealed interesting biological activities [2,3]. Besides the potential as new drugs, CDXs afford promising LC enantioresolution results [6].

In a continuation of our study, new enantiomerically pure CDXs were synthetized for biological activity evaluation as well as selectors for new CSPs, confirming that CDXs have important applications not only in the field of Medicinal Chemistry but also for analytical applications.

Acknowledgements:

This research was partially supported by the Strategic Funding UID/Multi/04423/2013 and UID/QUI/00062/2013 through national funds provided by FCT and ERDF, in the framework of PT2020, by projects PTDC/MAR-BIO/4694/2014 (reference POCI-01-0145-FEDER-016790; Project 3599-PPCDT), and 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, as well as by the Portuguese NMR Network, and CHIRALXANT-CESPU-2018.

[1] Shagufta, A.I. Eur. J. Med. Chem., 2016, 116, 267-280.

[2] Fernandes, C. et al. Bioorg. Med. Chem. 2014, 22, 1049-1062.

[3] Fernandes, C. et al. Pharmaceuticals, 2017, 10, 50, doi:10.3390/ph10020050.

[4] Phyo, Y.Z. et al. Molecules, 2018, 23, 142, doi:10.3390/molecules23010142.

[5] Carraro, M.L. et al. Chirality, 2017, 1–10

[6] Fernandes, C. et al. Chirality, 2017, 29(8),430-442.

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