Applied Chemistry


smallbutton_greenGROUP LEADER | MAJOR INTERESTS | RESEARCH TEAM | CURRENT PROJECTS | RELEVANT PUBLICATIONS

environmentalandappliedchemistry

GROUP LEADER 
Maria Elizabeth Tiritan | ORCID

 

MAJOR INTERESTS
We develop innovative chromatographic methods to quantify pharmaceuticals/organic compounds in the environmental, biological and pharmaceutical matrices. Biodegradation/degradation studies and identification of metabolites/transformation products is if of foremost importance. The investigation involving chirality and enantioselective in biological process is of major interest.

Specifically we aim at:

  • Development and validation methods by Liquid and Gas Chromatography to quantify drugs/pharmaceutical compounds in environmental and biological matrices;
  • Degradation/ biodegradation studies of pharmaceuticals;
  • Search for new metabolite/transformation products;
  • Chiral analyses.

 

RESEARCH TEAM

Researchers
Carla Fernandes | cfernandes@ff.up.pt | ORCID
Cláudia Maria Rosa Ribeiro | claudia.ribeiro@iscsn.cespu.pt | ORCID
Cristina Couto | cristina.couto@iscsn.cespu.pt | ORCID
Francisco Silva | francisco.silva@iscsn.cespu.pt | ORCID
Madalena Pinto | madalena@ff.up.pt | ORCID
Maria Elizabeth Tiritan | elizabeth.tiritan@iscsn.cespu.pt | ORCID
Nuno Milhazes | nuno.milhazes@iscsn.cespu.pt | ORCID

PhD Students
Alexandra Maia | xaninhamaia@gmail.com | ORCID

MSc Students
Cátia Sofia Rodrigues Silva | catisrs@hotmail.com
Maria Letícia Carraro | leticiacarraro@hotmail.com | ORCID

BSc Students
Vera Mónica da Silva Barbosa | verabarbose96@gmail.com | ORCID

Volunteers
Ana Sofia Costa | ana_sofia_mi@hotmail.com | ORCID
Ricardo Gonçalves | ricardodtgoncalves@gmail.com 
Sofia Manuela Moreira Dias | sofia_dias10@hotmail.com | ORCID

Research Technician
Virgínia Gonçalves | virginia.goncalves@cespu.pt | ORCID

 

CURRENT PROJECTS

Project PTDC/MAR-BIO/4694/2014 e POCI-01-0145-FEDER-016790: Navigating through marine-derived fungi: bioprospection and synthesis of bioactive secondary metabolites and analogues as chemotherapic agents | PI: Madalena Pinto | Team: Madalena Pinto, Alexandra Viana da Costa, Ana Catarina Alves, Ana Sara Gomes, Anake Kijoa, Carla Fernandes, Carlos Afonso, Chadaporn Prompanya, Cláudia Nunes, Cláudia Marques, Cláudia Bessa, Domingos Ferreira, Hassan Bousbaa, Honorina Cidade, Isabel Carvalho, Joana Fonseca, J. Soares, Liliana Raimundo, Lucília Saraiva, Lucinda Bessa, Maraia de Fátima Cerqueira, Salette Reis, Maria Elizabeth Tiritan, Emília Sousa, Eugénia Pinto, Maria Cruz, Marta Correia-da-Silva, Nelson Gomes, Silva, P., Paulo Costa, Sandra Marques, Sara Cravo, War Zin| Funding Entity: FEDERFCT | Period covered: 

The need for a continued search for new anti-infective and anticancer drugs is universally considered of great importance since many of the current drugs are insufficiently effective, highly toxic, and resistances may be developed. Our group has isolated two alkaloids, eurochevalierine, a potent inhibitor of the growth of human tumor cell lines [1], from the soil fungus Neosartorya pseudofischeri, and neofiscalin A from the soil and marine fungus N. siamensis with potent antibacterial activity [2]. Neofiscalin A exhibited also antibiofilm activity in both reference and multidrugs-resistant isolates, and is currently in the patent filing process. On the other hands, marine fungi derived xanthones, particularly yicathins and isomers were considered promising as chemotherapic agents [3]. So, eurochevalierine, neofiscalin A and yicathins can be considered very interesting models to discover new anti-infective and anticancer drugs to overcome drug-resistance that could represent innovative drug candidates. However, their availability to proceed to further investigations and their complex structures could limit their future as drug candidates. Our group has multi- and transdisciplinary skills, with a large experience in isolation and structure elucidation of natural products, synthesis, cellular and molecular biology and nanotechnology. Moreover, the synthesis of anti-infective [4,5] and antitumor [6-10] xanthone derivatives, particularly in multidrugs-resistant models [5,10], is the strength of our group. Therefore, this expertise can drive these natural products and derivatives with enough potency and selectivity to become new potential anti-infective/antitumor clinical candidates. However, our goal is not only to continue with the search for innovative marine-derived compounds but also to obtain derivatives/formulations of the most promising compounds to obtain more efficient analogues. To achieve these goals, five approaches will be undertaken: i) isolate other bioactive compounds from the marine-derived N. pseudofischeri and N. siamensis and other related strains; ii) synthesize eurochevalierine, neofiscalin A and yicathins to obtain more quantity of these products for in vitro and in vivo tests, iii) carry out successive molecular modifications in order to achieve more efficient analogues, iv) investigate their potential as anti-infective agents, v) perform in vitro studies in tumor cell lines; vi) incorporate in nanoparticles in order to improve permeability and selectivity of the most promising compounds. To carry out approach i) isolation of the bioactive metabolites, we will culture the fungi N. pseudofischeri and N. siamensis, isolated from the marine environment, such as sponge or coral to obtain eurochevalierine, neofiscalin A, and structurally related alkaloids. Moreover, we will also perform a co-culture of these two fungi with marine bacteria for the purpose of increasing the quantity of the alkaloids eurochevalierine and neofiscalin A as well as to verify if the fungi also accumulate other bioactive metabolites when compared to the pure cultures. To carry out approaches ii)-iii) these alcaloids and yicathins will be synthesized and the (semi)synthesized derivatives will be used to obtain a library of structurally-related analogues with improved efficacy. These results will allow us to establish structure activity relationships (SAR), to contribute to define the important molecular features of anti-infective and antitumor activities, and consequently, the design of more potent molecules. To carry out approach iv), the new compounds will be screened for antimicrobial activity using the agar disk diffusion assay and/or the broth microdilution method. These compounds will be also tested for their synergy with antibiotics, against isolates presenting resistance towards those antimicrobials, using the broth microdilution Checkerboard method. Compounds showing antimicrobial activity will be then tested for their ability to inhibit the biofilm formation. To screen for compounds with anti-parasitic activity their effect will be evaluated for Cryptosporidium inhibitory growth via human epithelial cells lines. To carry out approach v), the compounds will be screened for their in vitro growth inhibitory activity in human tumor cell lines. The elucidation of the molecular mechanism of antitumor activity of the most promising compounds will be performed, particularly alterations in cellular proliferation, cell cycle, mitosis, and apoptosis, analysis of the effect on tumor immune microenvironment, and identification of protein targets. To carry out approach vi), the compounds with promising anti-infective/antitumor activity will be incorporated into biodegradable and biocompatible LNP formulations by several methods, and technological parameters will be studied. This approach will allow us to verify if LNP formulations can improve the bioavailability and/or activity/selectivity of the bioactive compounds.


Project COXANT-CESPU-2016: Enantioselective synthesis of chiral xanthone derivatives and anti-inflammatory evaluation. | PI: Maria Elizabeth Tiritan | Team: Maria Elizabeth Tiritan, Carla Sofia Garcia Fernandes, Madalena Maria de Magalhães Pinto, Maria Letícia Carraro, Paolo De Marco | Funding Entity: CESPU | Period covered: 04-2016 to 03-2017

Cyclooxygenases (COX-1 and COX-2) are two important isoforms, in which, COX-2 is expressed in various pathophysiological processes, like inflammation and cancer. COX-2 has been identified as novel cancer chemo-preventive and therapeutic target being the searching of new COX-2 inhibitors of great interest. Xanthone derivatives and respective synthetic intermediates have demonstrated great potential as anti-inflammatory and anti-tumor agents. Recently in our group some chiral derivatives of xanthones (CDX) exhibited interesting dose-dependent growth inhibitory effects on the evaluated human tumor cell lines and enantioselectivity in some cases. In this project we aim to synthesize new CDX as single enantiomers and evaluate their anti-inflammatory activity. Moreover, in order to complement the search for enantioselectivity in biological activities, both enantiomers and the racemic mixture will be also evaluated as antimicrobial agents.


Project MYCO-CESPU-2016: Monitorization of mycotoxins and heavy metals in sediments of the estuaries of the Rivers Douro and Ave.|
PI: Cláudia Maria Rosa Ribeiro | Team: Cláudia Maria Rosa Ribeiro, Maria Elizabeth Tiritan, Ana Rita Ribeiro, Adrián Silva | Funding Entity: CESPU | Period covered: 04-2016 to 03-2017

Mycotoxins (MT) are toxic secondary metabolites produced by fungi that colonize a variety of cereals, fruits, vegetables or can occur in food and beverages under wet conditions during storage. These compounds are of significant health concern to both humans and animals because of their carcinogenicity and thus have been widely investigated in food commodities. Recently, MT have received considerable attention, since they have demonstrated to be part of the set of aquatic environmental contaminants. Aquatic environmental sources of MT can be the release from infected plants, manure from exposed livestock or effluents from urban waste water treatment plants. Since, these compounds have been found for the first time in Portuguese estuarine water samples, the aim of this study is to assess the spatial and temporal distribution of MT in sediment samples collected from the Douro and Ave Rivers. The results will provide important data for risk and possible toxicological effects and understanding the possible sources, routes and fates of these classes of pollutants in the Portuguese aquatic environment.

 

RELEVANT PUBLICATIONS

Moreira IS, Amorim CL, Ribeiro AR, Mesquita RBR, Rangel AOSS, van Loosdrecht MCM, Tiritan ME, Castro PML

.2015

. Removal of fluoxetine and its effects in the performance of an aerobic granular sludge sequential batch reactor. (Journal Article)

J Hazard Mater, 287C pp. 93–101.DOI: 10.1016/j.jhazmat.2015.01.020.

(BibTeX)

Ribeiro AR, Maia AS, Cass QB, Tiritan ME

.2014

. Enantioseparation of chiral pharmaceuticals in biomedical and environmental analyses by liquid chromatography: an overview. (Journal Article)

J Chromatogr B Analyt Technol Biomed Life Sci, 968 pp. 8–21.DOI: 10.1016/j.jchromb.2014.02.049.

(BibTeX)

Ribeiro AR, Santos LHMLM, Maia AS, Delerue-Matos C, Castro PML, Tiritan ME

.2014

. Enantiomeric fraction evaluation of pharmaceuticals in environmental matrices by liquid chromatography-tandem mass spectrometry. (Journal Article)

J Chromatogr A, 1363 pp. 226–235.DOI: 10.1016/j.chroma.2014.06.099.

(BibTeX)

Moreira IS, Ribeiro AR, Afonso CM, Tiritan ME, Castro PML

.2014

. Enantioselective biodegradation of fluoxetine by the bacterial strain Labrys portucalensis F11. (Journal Article)

Chemosphere, 111 pp. 103–111.DOI: 10.1016/j.chemosphere.2014.03.022.

(BibTeX)

Amorim CL, Maia AS, Mesquita RBR, Rangel AOSS, van Loosdrecht MCM, Tiritan ME, Castro PML

.2014

. Performance of aerobic granular sludge in a sequencing batch bioreactor exposed to ofloxacin, norfloxacin and ciprofloxacin. (Journal Article)

Water Res, 50 pp. 101–113.DOI: 10.1016/j.watres.2013.10.043.

(BibTeX)

Maia AS, Ribeiro AR, Amorim CL, Barreiro JC, Cass QB, Castro PML, Tiritan ME

.2014

. Degradation of fluoroquinolone antibiotics and identification of metabolites/transformation products by liquid chromatography-tandem mass spectrometry. (Journal Article)

J Chromatogr A, 1333 pp. 87–98.DOI: 10.1016/j.chroma.2014.01.069.

(BibTeX)

Couto CMCM, Pinto I, Madureira TV, Rocha MJ, Tiritan ME, Lopes JA, Almeida AA

.2014

. Lower Douro River basin (Portugal) water quality – Focus on trace element changes and anthropogenic sources of contamination (Proceeding)

,Global NEST Journal.

(BibTeX)

Ribeiro AR, Maia AS, Moreira IS, Afonso CM, Castro PML, Tiritan ME

.2014

. Enantioselective quantification of fluoxetine and norfluoxetine by HPLC in wastewater effluents. (Journal Article)

Chemosphere, 95 pp. 589–596.DOI: 10.1016/j.chemosphere.2013.09.118.

(BibTeX)

Ribeiro C, Ribeiro AR, Maia AS, Gonçalves VMF, Tiritan ME

.2014

. New trends in sample preparation techniques for environmental analysis. (Journal Article)

Crit Rev Anal Chem, 44 (2), pp. 142–185.DOI: 10.1080/10408347.2013.833850.

(BibTeX)

Ribeiro AR, Afonso CM, Castro PML, Tiritan ME

.2013

. Enantioselective biodegradation of pharmaceuticals, alprenolol and propranolol, by an activated sludge inoculum. (Journal Article)

Ecotoxicol Environ Saf, 87 pp. 108–114.DOI: 10.1016/j.ecoenv.2012.10.009.

(BibTeX)

Madureira TV, Rocha MJ, Cruzeiro C, Rodrigues I, Monteiro RAF, Rocha E

.2012

. The toxicity potential of pharmaceuticals found in the Douro River estuary (Portugal): evaluation of impacts on fish liver, by histopathology, stereology, vitellogenin and CYP1A immunohistochemistry, after sub-acute exposures of the zebrafish model. (Journal Article)

Environ Toxicol Pharmacol, 34 (1), pp. 34–45.DOI: 10.1016/j.etap.2012.02.007.

(BibTeX)

Ribeiro AR, Castro PML, Tiritan ME

.2012

. Chiral pharmaceuticals in the environment (Journal Article)

Environmental Chemistry Letters, 10 (3), pp. 239–253, ISSN: 1610-3661.DOI: 10.1007/s10311-011-0352-0.

(BibTeX)

Ribeiro AR, Gonçalves VMF, Maia AS, Carvalho MF, Castro PML, Tiritan ME

.2012

. Microbial degradation of pharmaceuticals followed by a simple HPLC-DAD method. (Journal Article)

J Environ Sci Health A Tox Hazard Subst Environ Eng, 47 (13), pp. 2151–2158.DOI: 10.1080/10934529.2012.696422.

(BibTeX)

Madureira TV, Rocha MJ, Cruzeiro C, Galante MH, Monteiro RAF, Rocha E

.2011

. The toxicity potential of pharmaceuticals found in the Douro River estuary (Portugal): assessing impacts on gonadal maturation with a histopathological and stereological study of zebrafish ovary and testis after sub-acute exposures. (Journal Article)

Aquat Toxicol, 105 (3-4), pp. 292–299.DOI: 10.1016/j.aquatox.2011.06.017.

(BibTeX)

Madureira TV, Cruzeiro C, Rocha MJ, Rocha E

.2011

. The toxicity potential of pharmaceuticals found in the Douro River estuary (Portugal)--experimental assessment using a zebrafish embryo test. (Journal Article)

Environ Toxicol Pharmacol, 32 (2), pp. 212–217.DOI: 10.1016/j.etap.2011.05.005.

(BibTeX)

Madureira TV, Barreiro JC, Rocha MJ, Rocha E, Cass QB, Tiritan ME

.2010

. Spatiotemporal distribution of pharmaceuticals in the Douro River estuary (Portugal). (Journal Article)

Sci Total Environ, 408 (22), pp. 5513–5520.DOI: 10.1016/j.scitotenv.2010.07.069.

(BibTeX)

Madureira TV, Barreiro JC, Rocha MJ, Cass QB, Tiritan ME

.2009

. Pharmaceutical trace analysis in aqueous environmental matrices by liquid chromatography-ion trap tandem mass spectrometry. (Journal Article)

J Chromatogr A, 1216 (42), pp. 7033–7042.DOI: 10.1016/j.chroma.2009.08.060.

(BibTeX)