Group Coordinator: Maria Teresa Duarte


The group’s objectives are grounded on existing skills, recognized accomplishments and on-going state-of-the-art research. Moreover, as applied to bioactive molecules, they amply meet the general goal of CQE by addressing the study of compounds along the ‘design – synthesis – properties – function/applications’ ladder. The major objectives are:


General perspective of the laboratoryA wide range of chemical structures with potential therapeutic value (eg, as antitumor, antiviral or antibacterial agents) and ranging from classical organic, coordination and organometallic compounds to supramolecular entities (eg, BioMOFs) are synthesized. The designing approaches primarily involve bioisosteric replacement tactics on pre-validated lead pharmacophores, including chiral scaffolds (eg, carbohydrates, camphor-derived ligands, and macrocyclic natural products or their analogues). The synthetic efforts involve concomitant research into efficient, often unconventional and/or eco-friendly synthetic strategies. Examples are biomimetic oxidations by chemical analogues of ubiquitous enzymes and laccase-mediated oxidations. As part of the overall goal, structure-activity relationships are assessed for the novel drug candidates. Within the scope of existing collaborations, the initial test systems may include human biotransformation-competent tester bacteria, specific cell lines and, when justified by promising in vitro data, evaluation in suitable rodent models.


IMG_3747A major goal involves exploring crystal engineering in the search for novel API crystal forms (co-crystals, salts, solvates) to tailor their properties for improved in vivo performance (stability, solubility, bioavailability) or extended shelf life. This includes a quest for control and/or avoidance of polymorphisms using ionic liquids (ILs) either as solvents or in API-IL ion pairs. In addition, controlled drug transport and release are sought by designing BioMOFs containing APIs as ligands or guests; the synthetic approaches involve environment-friendly synthetic mechanochemistry and microwave techniques. Structural and molecular mobility studies on amorphous APIs are also performed using non-destructive techniques (SS-NMR, DRX) complemented with thermal stability studies, as a contribution to model APIs with higher bioavailability. This approach is also applied to common amorphous API-excipient and co-amorphous API combinations.


IMG_3546The group’s expertise in assessing the effects of bioactivation of endogenous and xenobiotic molecules, anchored on the ability to synthesize biomarker standards and develop/validate sensitive analytical methodologies, is primarily directed towards: 1) Use of proteomics tools to develop early tumor initiation biomarkers, on the premise that covalent histone modification by metabolically activated chemical carcinogens triggers epigenetic alterations that are at the origin of chemically-induced cancers; 2) Use of proteomics tools to assess the role of estrogen-modified proteins in the onset of diseases that are more common in women; 3) Development of NMR-based in vitro methods to predict the skin sensitization potential of allergenic agents, using HR-MAS in reconstructed epidermal cells to monitor the formation of covalent adducts between chemical toxicants (and/or their electrophilic metabolites) and nucleophilic residues in proteins. Given the REACH regulation, this goal is of great significance to European cosmetic and pharmaceutical industries.

Additional themes are:

– Use of a 1H-NMR-based metabolomic approach coupled with multivariate statistical analysis to assess quantitatively the response of the exo- and endo-metabolome of yeast cells to chemical stress agents.

– Use of MS tools to characterize in-process impurities and degradation products of APIs and predict their biological safety.

Photos from our labs


Group photo


Integrated Members

Alexander Kirillov

Alexandra Maria Moita Antunes

Ana Cristina da Silva Fernandes


Cristina Isabel da Costa Jacob

Hermínio Albino Pires Diogo

Joao Paulo Nunes Cabral Telo

José do Rosário Ascenso

Maria da Conceição Oliveira

Maria de Fátima Minas da Piedade

Maria Fernanda Neves Carvalho

Maria Matilde Duarte Marques

Maria Paula Alves Robalo

Maria Teresa Leal da Silva Duarte

Maria Teresa Nunes

Marina Kirillova

Paula Maria de Jorge Marcos

Vânia Mafalda de Oliveira André


Other PhD Members

Ana Catarina Cardoso de Sousa

Ana Sofia Diogo Ferreira

Bernardo Jerosch Herold

Clementina Maria Cardoso Teixeira da Cunha Pereira

[Dulce Elisabete Bornes Teixeira Pereira Simão

João Luís Alves Ferreira da Silva

José Gonçalo Deira Duarte de Campos Justino

Mª Cristina Froes Brilhante Dias Gomes de Azevedo

Mª João Gomes Ferreira

Pedro Paulo de Lacerda e Oliveira Santos


Other researchers

Álvaro Moneo Marín

Ana Lúcia Aguiar Godinho

Ana Maria da Cruz Dias

Ana S.O. Knittel

Catarina Sofia Romão Charneira

Emanuel Fonseca Dinis Costa

Filipa Isabel Ferreira Galego

Filipa João Fernandes Ramilo Gomes

Inês Catarina Batista Martins

Inês Sofia Lança Martins

Ivânia Raquel Costa Cabrita

Joana Raquel Antunes Paulino

Joana Rita Maia Bernardo

João M.S. Cardoso

João Martinho Silva Ramalho Cardoso

João Pedro da Costa Nunes

Pedro Boto Pereira Franco Pinheiro

Pedro Ricardo da Rocha Florindo

Rodrigo Pereira Santos

Shrika Harjivan

Sílvia Andreia Almeida Quaresma

Sofia Leonor Afonso Domingos

Micael Alexandre Santos Miranda



Alexandra P.S. Roseiro

André Pedroso Ferreira

Ana Borlido Claro dos Santos

Ana Cláudia Pereira Cerdeira

Ana Isabel Real Maças

Emanuel Dinis Costa

Marta Martins

Miguel António Ricardo Bispo

Punil Sanatcumar

Ricardo Manuel Picciochi de Oliveira

Tiago Daniel Adriano Fernandes

Sara Cristina Alves de Sousa

Susana Silva Pinto



1. André, V.; Braga, D.; Grepioni, F.; Duarte, M.T. (2009) Crystal forms of the antibiotic 4-aminosalicylic acid: solvates and molecular salts with dioxane, morpholine and piperazine; Crystal Growth & Design, 9, 5108-51116. DOI: 10.1021/cg900495s

2. Ferreira, A.P.; Ferreira da Silva, J.L.; Duarte, M.T.; Piedade, M.F.M.; Robalo, M.P.; Harjivan, S.G.; Marzano, C.; Gandin, V.; Marques, M.M. (2009) Synthesis and characterization of new organometallic benzo[b]thiophene derivatives with potential antitumor properties; Organometallics, 28, 5412-5423. DOI: 10.1021/om9003835

3. Pereira, L.; Coelho, A.V.; Viegas, C.A.; Ganachaud, C.; Lacazio, G.; Tron, T.; Robalo, M.P.; Martins, L.O.M. (2009) On the mechanism of biotransformation of the anthraquinonic dye Acid Blue 62 by laccases; Adv. Synth. Cat., 351, 1857-1865. DOI: 10.1002/adsc.200900271

4. Antunes, A.M.M.; Godinho, A.L.A.; Martins, I.L.; Oliveira, M.C.; Gomes, R.A.; Coelho, A.V.; Beland, F.A.; Marques,M.M. (2010) Protein adducts as prospective biomarkers of nevirapine toxicity; Chem. Res. Toxicol., 23, 1714-1725. DOI: 10.1021/tx100186t

5. André, V., Hardeman, A., Halasz, I., Stein, R.S., Jackson, G.J., Reid, D.G., Duer, M. J., Curfs, C., Duarte, M.T., Frišcic, T. (2011) Mechanosynthesis of the metallodrug bismuth subsalicylate from Bi2O3 and the first structural characterisation of a bismuth salicylate; Angew. Chem.-Int. Edit., 50, 7858-7861. DOI: 10.1002/anie.201103171

6. Lourenço, A.B.; Ascenso, J.R.; Sá-Correia, I. (2011) Metabolic insights into the yeast response to propionic acid based on high resolution 1H NMR spectroscopy; Metabolomics, 7, 457-468, 2011. DOI 10.1007/s11306-010-0264-1

7. Picchiochi; R.; Diogo, H.P.; Minas da Piedade, M.E. (2011) Thermodynamic characterization of three polymorphic forms of piracetam; J. Pharm. Sci., 100, 594-603. DOI: 10.1002/jps.22294

8. Caixas, U.; Antunes, A.M.M.; Marinho, A.T.; Godinho, A.L.A.; Grilo, N.M.; Marques, M.M., Oliveira, M.C.; Branco, T.; Monteiro, E.C.; Pereira, S.A. (2012) Evidence for nevirapine bioactivation in man: searching for the first step in the mechanism of nevirapine toxicity; Toxicology, 301, 33-39. DOI: 10.1016/j.tox.2012.06.013

9. Charneira, C.; Grilo, N.M.; Pereira S.A.,; Godinho, A.L.A.; Monteiro, E.C.; Marques, M.M.; Antunes, A.M.M. (2012) N-terminal valine adduct from the anti-HIV drug abacavir in rat hemoglobin as evidence for abacavir metabolism to a reactive aldehyde in vivo; Br. J. Pharmacol., 167, 1353-1361. DOI: 10.1111/j.1476-5381.2012.02079.x

10. Wanke, R.; Novais, D.A.; Harjivan, S.G; Marques, M.M.; Antunes, A.M.M. (2012) Biomimetic oxidation of aromatic xenobiotics: synthesis of the phenolic metabolites from the anti-HIV drug Efavirenz, Org. Biomol. Chem., 10, 4554-4561. DOI: 10.1039/c2ob25212k. HOT ARTICLE.