The BIOIN group is constituted by two main sub-groups, each associated to a distinct faculty of the UL, one geographically located at Instituto Superior Técnico (CQE@tecnico) and the one at Faculdade de Ciências (CQE@ciencias)
Group Coordinator: João Emídio da Silva da Costa Pessoa in CQE@tecnico & CQE@ciencias
Group Coordinator in CQE@ciencias: M. Helena Garcia
The core research at Bioinorganic Chemistry and Drug Development Group (BIOIN) is to understand the role that metal ions have on biological phenomena, and how they can be of use to propose answers to society challenges. In this context, metal complexes and/or organic compounds are designed to interact with biologically relevant molecules forming metal complexes. From this perspective, the group uses coordination and organometallic chemistry as a tool to give answers to significant biological issues and medicinal problems, by developing prospective therapeutic or diagnostic agents.
The research strategy of the group is the synthesis of ligands and metal complexes (MCs) pursuing a biotarget- or mechanism-based approach, followed by their thorough characterization including chemical stability in aerobic and aqueous media (as typically required for medicinal applications). The most suitable compounds are bio-assayed and whenever meaningful subjected to structure-activity relationships. The seek for desirable effective biomedical drugs usually requires a combination of physical, chemical, biological and computational approaches; spectroscopy, crystallography and computational techniques (such as DFT, molecular mechanics/molecular dynamics and docking to proteins) are tools usually applied to determine the structural and functional properties. Several synthetic methods are also used for the design and assembly of structural, supramolecular, spectroscopic and functional models of the metal site in enzymatic systems.
Besides bioinorganic and drug development objectives, the sub-group at CQE@tecnico has also been active in creating bio-inspired catalysts to obtain several types of fine chemicals. Some of the metal complexes were supported in polymer matrixes or encapsulated in zeolites. Moreover the advantage of being recyclable, in some way these systems can also mimic the environment of enzymes.
Besides bio-organometallic chemistry the sub-group at CQE@ciencias has also been designing and synthesizing metal complexes for non-linear optical materials and maintained several international collaborations in this subject.
The Group encompasses expertise mostly on:
– Synthesis of organic, coordination and organometallic compounds
– Development of therapeutic and diagnostic agents
-Speciation studies, namely in models of biological media, using potentiometry and spectroscopic techniques, with an integrative perspective, to fully understand structure-bioactivity relationships
– Speciation of metallodrugs in the human blood using ion chromatography coupled to ICP-MS
– DFT, molecular mechanics, molecular dynamics and docking of proteins computational studies
– Bioavailability and transport of metal complexes (MCs) in blood and biological fluids, to assess their therapeutic potential and/or toxicity and/or uptake by cells
– Bio-inspired catalysis modeling structural and functional models of enzymes
– Design of ligands to target metalloproteins and tune their therapeutic action
The members of the BIOIN Group are highly motivated to:
- undertake new initiatives and support joint research in the fields of Bio-inorganic Chemistry and Drug Development and Pharmaceutical Sciences – seek innovative strategies to achieve the designed specific objectives
– encourage studies involving new types of coordination and organometallic compounds
– develop research on the toxicity and safety of chemical substances containing metal complexes, supporting the implementation of the European REACH regulations
– encourage exchange of expertise and transfer of knowledge and technology with the industrial sector, also seeking innovative approaches of collaboration
– strengthen the cooperation between its members and promote interdisciplinary studies and joint initiatives with the other Groups of CQE and other Units.
The specific objectives of BIOIN include:
A1. adequate anti-cancer, anti-parasitic and anti-tuberculosis compounds (namely providing different mechanisms of action, wider spectrum of activity, as well as showing lower toxicity to normal cells)
A2. enzyme inhibitors and anti-neurodegenerative compounds – polyfunctional compounds with targeting groups and pharmacophores to interfere with the action of specific biomolecules
A3. suitable chelating agents to interact with or to sequester metals in the body for decorporation, redistribution or passivation of misplaced/aberrant metal ions.
B. Connecting the structure to their biological function of the novel bio-active compounds by:
B1. In silico pre-scanning of the bio-activity of prospective drugs designed by fragment/mechanism-base approaches
B2. Evaluation of the interaction of ligands and MCs with bio-macromolecules (namely DNA, matrix metalloproteinases and other proteins involved in specific metabolic and pathological features of target cells and disease pathways)
B3. Elucidation of the transport in blood of therapeutic MCs and study their uptake by cells
B4. Speciation of MCs in biological fluids and inside cells
B5. Binding and interaction of ionic liquids with DNA and proteins and subsequent changes of structure and function of these biomolecules
B6. Establishment of structure-activity relationships for defined groups of MCs towards specific cell lines and in vivo (in collaboration)
C. Bio-inspired metal mediated synthesis or catalysis:
C1. Model metal sites of metalloenzymes namely to obtain chiral or non-chiral molecules relevant for the synthesis of therapeutic drugs, improving currently used synthetic methods
C2. Model metal sites of metalloenzymes namely to obtain chiral or non-chiral molecules industrially relevant, improving currently used synthetic methods
BIOIN in CQE@tecnico
João Emídio da Silva da Costa Pessoa
Maria Amélia Loureiro Santos Seabra
José Armando Luísa da Silva
Sílvia de Vasconcelos Chaves
Maria Isabel Rodrigues Correia
Pedro Miguel Santos Ferreira Adão
Isabel Cavaco (PhD, Univ of Algarve)
Karam Chand (2014-2016)
Ranganath Keri (2014-2015)
Cristina Pereira de Matos
Carlos Manuel Brandão Teixeira
Anna Irto (2015-2016)
Hesham Alsoghier (2015)
Ana Franco (in collaboration with CQFM)
Daniel TomazSara Conchinhas
Elisa Bernardini (2015-2016)
Rosita Cappai (2016-2017)
Collaborators & Other researchers
Filipa R. Gomes (M.Sc.)
Nádia Ribeiro (M.Sc.)
Luca Piemontese (PhD, Research Fellow, Univ Bari)
BIOIN in CQE@ciencias
Maria Helena Anselmo Viegas Garcia (Associate Professor)
Ana Isabel Antunes Tomaz Diniz (Assistant Researcher)
Andreia Marques Valente (Assistant Researcher)
Tânia Sofia Morais (PostDoc researcher)
Leonor Côrte-Real (M.Sc.)
Collaborators & Other researchers
Maria José Villa de Brito (Auxiliar Professor, FCUL)
Anabela Sanchez (M.Sc.) – Grantee
Ana Sofia Assis (M.Sc.) – Grantee
Adhan Pilon (M.Sc.) – Grantee
Andreia Carvalho (M.Sc. student, FCUL)
Inês Pereira (M.Sc. student, FCUL)
Ricardo Teixeira (M.Sc. student, FCUL)
Bebiana Pinto (M.Sc. student, FCUL)
David Alves (M.Sc. student, FCUL)
Patrícia Gírio (M.Sc. student, FCUL)
Karolina Bartkowiak (Erasmus student)
Tiago Moreira (M.Sc. student, Univ. Minho)
Ana Rita Brás (M.Sc. student, Univ. Minho)
Fernanda Marujo Marques ( Researcher, C2TN-IST)
Paulo Mendes (Prof. Univ. Évora)
C. Acilan, Z. Adiguzel, B. Cevatemre, D. Karakas, E. Ulukaya, N. Ribeiro, I. Correia, J. Costa Pessoa, “Synthesis, biological characterization and evaluation of molecular mechanisms of novel copper complexes as anticancer agents“, Biochem. Biophys. Acta – Gen Subj, 2016, in press.
S. Barroso, P. Adão, A.M. Coelho, J. Costa Pessoa, A.M. Martins, “Pinacol coupling of benzaldehydes mediated by titanium complexes displaying amine bis(phenolate) ligands“, J. Mol. Catal. A: Chemical, 2016, 412, 107-116.
J. Costa Pessoa, S. Etcheverry, D. Gambino, “Vanadium compounds in medicine”, Coord. Chem. Rev., 2015, 301–302, 24-48.
C. Quintanova, R. S. Keri, S. M. Marques, M. G-Fernandes, S. M. Cardoso, M. L.Serralheiro, M. A. Santos. “Design, Synthesis and bioevaluation of Tacrine-Cinnamate based hybrids as Potential Bifunctional Anti-Alzheimer Drug Candidates”, Med. Chem. Comm., 2015, 6, 1969-1977.
K. Chand, H. M. Alsoghiera, S. Chaves, M. A. Santos, “Tacrine-(hydroxybenzoyl-pyridone) hybrids as potential multifunctional anti-Alzheimer´s agents: AChE inhibition, antioxidant activity and metal chelating capacity“, J. Inorg. Biochem. 2016, 163, 266-277
A. Hiremathad, K. Chand, A. R. Esteves, S. M. Cardoso, R. R. Ramsay, S. Chaves, R. S. Keri, M. A. Santos. “Tacrine-allyl/propargylcysteine-benzothiazole trihybrids as potential anti-Alzheimer´s drug candidates“, RSC Adv, 2016, 6, 53519-53532
N. Mendes, F. Tortosa, A. Valente, F. Marques, A. Matos, T. S. Morais, A.I. Tomaz, F. Gärtner, M. H. Garcia, “In vivo Performance of a Ruthenium-cyclopentadienyl Compound in an Orthotopic Triple Negative Breast Cancer Model”, Anti-cancer Agents in Medicinal Chemistry Vol. 17, No. 1, 2017 doi: 10.2174/1871520616666160922165133.
T. S. Morais, A. Valente, A. I. Tomaz, F. Marques, M. H. Garcia, “Tracking anti-tumor metallodrugs: promising agents with the Ru(II)- and Fe(II)-cyclopentadienyl scaffolds”, Fut. Med. Chem. 2016, 8, 527-544. (Selected as Issue Special Report. DOI: 10.4155/fmc.16.7)
L.Côrte-Real, F. Marques, M. P. Robalo, G.Nogueira, F. Avecilla, F.C. Santos, A. I. Tomaz, M. H. Garcia, A. Valente, “The significant role of coligands in novel ruthenium(II)-cyclopentadienyl bipyridine derivatives: ranging from non-cytotoxic to highly cytotoxic compounds”, J. Inorg. Biochem., 2015, 150, 148–159.
M. Domarus, M. L. Kuznetsov, J. Marçalo, A. J. L. Pombeiro, J.A.L. da Silva, “Amavadin and Homologues as Mediators of Water Oxidation” Angew. Chem., Int. Ed., 2016, 55, 1489-1492;