CNC

Job Opportunities | Privacy Policy | Contacts

Biotechnology

Medicinal Chemistry and Drug Discovery

The aim of our research is to study the medicinal chemistry of the diterpenoids, namely carnosic acid, oridonin and their derivatives, as well as triterpenoids such as celastrol, madecassic acid, and derivatives and to study the anticancer activity of these compounds.

Computer assisted drug discovery (CADD) will be used to support the development of new drugs acting on ubiquitin-proteasome system (UPS) with potent anticancer activity. In addition we have also been involved in studies on pharmacophore and structure-based drug discovery for the rational design of lead compounds inhibitors of BACE1 and Glutaminyl Cyclase for Alzheimer’s disease treatment.

Our research is also devoted to exploring the medicinal chemistry of the diterpenoids, namely the resin acids and their derivatives. We identify hit compounds to drive drug discovery campaigns, chemical probes to study biological processes and devise shorter, more-efficient semi-synthetic routes towards naturally occurring compounds. In addition, we exploit the potential of the diterpenoids in the development of bio-based antimicrobial surfaces.

Additional objectives are to understand in depth at the molecular level the mechanisms of antimicrobial resistance, their incidence and dissemination to pave ways of fighting this huge problem of the present century, namely, to overcome resistance by investigate new therapeutic alternatives and discover novel antibacterials.

Another important topic of interest is to study neglected tropical diseases (NTDs) caused by pathogens parasites Leishmania, Trypanossoma and Giardia lamblia, to understand host-parasite interaction and to discover potential new drugs and therapeutic strategies to treat these infectious diseases.

Keywords

-   Compound design & synthesis

-   Terpenoids

-   Cancer

-   Antimicrobial resistance

-   Protozoan infections

Research Lines

1 - Rational design, synthesis and biological evaluation of new anticancer drugs (PI Jorge A.R. Salvador)

2 - Discovery of new drugs assisted by computer assisted drug discovery (CADD) (PI Jorge A.R. Salvador)

3 - Design & synthesis of antimicrobial agents and materials (PI Vânia M. Moreira)

4 - Molecular characterization of multidrug resistant bacteria and therapeutic strategies (PI Gabriela Silva)

5 - New therapeutic strategies in neglected parasitic diseases (PI Maria do Céu Sousa)

Selected Publications

Hassan, H., Forsman, N., Wan, X., Keurulainen, L., Bimbo, L. M., Stehl, S., van Charante, F., Chrubasik., M., Prakash, A., Johansson, L.-S., Mullen, D. C., Johnston, B., Zimmermann, R., Werner, C., Yli-Kauhaluoma, J., Coenye, T., Saris, P. E. J., Österberg, M., Moreira, V. M.* Non-leaching, highly biocompatible nanocellulose surfaces that efficiently resist fouling by bacteria in an artificial dermis model, ACS APPL. BIO MATERIALS, 2020, 3: 4095-4108, doi: 10.1021/acsabm.0c00203.

Clarissa Perez Faria, Bruno Miguel Neves, Ágata Lourenço, Maria Teresa Cruz, João D Martins, Ana Silva, Sónia Pereira, Maria do Céu Sousa*. 2020. Giardia lamblia Decreases NF-κB p65RelA Protein Levels and Modulates LPS-Induced Pro-Inflammatory Response in Macrophages. Scientific Reports, 10: 6234. doi: https://doi.org/10.1038/s41598-020-63231-0

Hassan, G.; Forsman, N.; Wan, X.; Keurulainen, L.; Bimbo, L. M.; Johansson, L.-S.; Sipari, N., Yli-Kauhaluoma, J.; Zimmermann, R., Stehl, S.; Werner, C.; Saris, P. E. J., Österberg, M.; Moreira, V. M.*, Dehydroabietylamine-based Cellulose Nanofibril Films: A new Class of Sustainable Biomaterials for Highly Efficient, Broad-Spectrum Antimicrobial Effects, ACS SUSTAINABLE CHEM. ENG, 2019, 7: 5002-5009, doi: 10.1021/acssuschemeng.8b05658.

Domingues S, Rosário N, Cândido Â, Neto D, Nielsen KM, Da Silva GJ. (2019). Competence for natural transformation is common among clinical strains of resistant Acinetobacter spp. Microorganisms, 7, 30. doi:103390/microorganisms7020030

Valdeira ASC, Darvishi E, Woldemichael GM, Beutler JA, Gustafson KR, Salvador JAR*. Madecassic Acid Derivatives as Potential Anticancer Agents: Synthesis and Cytotoxic Evaluation. J Nat Prod. 2019 Aug 23;82(8):2094-2105. doi: 10.1021/acs.jnatprod.8b00864.

Ana S. C. Valdeira, Daniel A. Ritt, Deborah K. Morrison, James B. McMahon, Kirk R. Gustafson and Jorge A. R. Salvador*, Synthesis and Biological Evaluation of New Madecassic Acid Derivatives Targeting ERK Cascade Signaling, Frontiers in Chemistry, 28 September 2018, DOI: 10.3389/fchem.2018.00434.

Acúrcio RC, Scomparin A, Conniot J, Salvador JAR, Satchi-Fainaro R, Florindo HF, Guedes RC. Structure-Function Analysis of Immune Checkpoint Receptors to Guide Emerging Anticancer Immunotherapy. J Med Chem. 2018 Dec 27;61(24):10957-10975. doi: 10.1021/acs.jmedchem.8b00541

Sandra A.C.Figueiredo, Jorge A.R. Salvador*, Roldán Cortés, Marta Cascante, Design, synthesis and biological evaluation of novel C-29 carbamate celastrol derivatives as potent and selective cytotoxic compounds, European Journal of Medicinal Chemistry, Vol139, 20 Oct 2017, Pag 836-848. DOI: 10.1016/j.ejmech.2017.08.058

Sousa M.C,* Varandas R., Santos R.C., Santos-Rosa M, Alves V. Salvador J.A.R.* 2014. “Antileismanial activity of semisynthetic lupane triterpenoids betulin and betulinic acid derivatives: synergistic effects with miltefosine”, Plos One 18; 9(3):e89939. doi:10.1371/journal.pone.0089939

Salvador J. A. R.,* Carvalho J. F. S., Leitão A. J., Neves M. A. C., Silva M. M. C., Silvestre S. M., Sá e Melo, M. L. Anticancer steroids: linking natural and semi-synthetic compounds. Natural Product Reports, 2013, 30, 324-374. doi: 10.1039/C2NP20082A

Salvador J. A. R.,* Moreira V. M., Gonçalves B. M. F., Leal A. S. M., Jing Y. Ursane-type pentacyclic triterpenoids as useful platforms to discover anticancer drugs. Natural Product Reports, 2012, 29, 1463-1479. doi: 10.1039/C2NP20060K.

S. Domingues, K. Harms, W.F. Fricke, P.J. Johnsen, G.J. da Silva, K.M. Nielsen. (2012) Natural transformation facilitates transfer of transposons, integrons and gene cassettes between bacterial species. PLoS Pathog. 8(8): e1002837. doi:10.1371/journal.ppat.1002837

Ongoing Research Projects

Diterpenoid-based scaffolds for enabling skin repair (DipSkinRepair). Tenovus Scotland (project S18-23), Feb 2019- Aug 2021 (PI Vânia M. Moreira)

Giardia lamblia extracellular vesicles in modulation of host immune cells: potential application of Giardia EVs against intestinal inflammation. SAU-PAR/31506/2017, ( PI Maria do Céu Sousa)

Horizontal gene transfer of colistin resistance and virulence co-regulation in Salmonella enterica and Escherichia coli from animals and meat products. PhD grant, supervisor Gabriela Silva)

Projetos de Desenvolvimento e Implementação de Infraestruturas de Investigação inseridas no RNIE. Rede Nacional de Espectrometria de Massa. Nó da UC. Janeiro de 2017-jan 2021, (PI Jorge A. R. Salvador)

2014-2020 Small-molecule inhibitors of human proteasome: a step forward in anticancer drug discovery Ref: PTDC/QEQ-MED/7042/2014 (Co-PI Jorge A. R. Salvador)

External collaborations

Marta Cascante, Universitat de Barcelona
Faculty of Biology (IBUB), Dept Biochemistry and Molecular Biomedicine, http://www.bq.ub.es/bioqint/principaleng.html

Varsha Gandhi, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, https://faculty.mdanderson.org/profiles/varsha_gandhi.html

Karen T. Liby - Department of Pharmacology and Toxicology, Michigan State University, 1355 Bogue Street, East Lansing, MI, 48824, USA libykare@msu.edu, https://phmtox.msu.edu/people/faculty/liby/

Jari Yli-Kauhaluoma, Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland; jari.yli-kauhaluoma@helsinki.fi, https://researchportal.helsinki.fi/en/persons/jari-yli-kauhaluoma

Kaare M. Nielsen, Oslo Metropolitan University, Norway. https://www.oslomet.no/en/about/employee/kamni/

Constança Pomba, Faculty of Veterinary Medicine of the University of Lisbon, Portugal, http://www.fmv.ulisboa.pt/pt/investigacao/ciisa

Graziela Zanini, Instituto Nacional de Infectologia Evandro Chagas da Fundação Oswaldo Cruz do Rio de Janeiro (INI/FIOCRUZ) do Brasil. https://www.ini.fiocruz.br/parasitologia.html

Simona Collina (Facoltà di Farmacia, Universita’ Degli Studi Di Pavia, Dip.to Scienze del Farmaco, Italy. http://scienzedelfarmaco.unipv.it/

Jorge Salvador

PhD, Group Leader

Alcino Leitão

PhD, Assistant Prof.

Gabriela Silva

PhD, Associate Prof.

Mª Céu Sousa

PhD, Assistant Prof.

Sara Domingues

PhD, Assistant Prof.

Clarissa Perez Faria

PhD, Researcher

Vânia Moreira

PhD, Assistant Prof.

Sofia Anastácio

PhD, Private Sector

Ágata Lourenço

PhD Student

Judite Coimbra

PhD Student

Daniela Alho

PhD Student

Sara Moura

PhD Student

Pedro Fernandes

PhD Student

Tiago Lima

PhD Student

Pedro Sobral

PhD Student

GROUP LEADER AND PRINCIPAL INVESTIGATOR

Jorge Salvador, PhD

ORCID

CiênciaID

Jorge Salvador has a degree in Pharmaceutical Sciences, (University of Coimbra) a master’s degree in Organic & Technological Chemistry, (New University of Lisbon) and a Ph.D. in Pharmacy-Pharmaceutical Chemistry (Univ. Coimbra in collaboration with the University of York, U.K.). He spent one year as a Pos-doc student at the University of Sussex, UK. Postgrad HICR- Cancer Biology & Therapeutics from Harvard-Medical School, University of Harvard, USA. He has a position as Full Professor at Faculty of Pharmacy, University of Coimbra.

PRINCIPAL INVESTIGATOR

Vânia Moreira, PhD

ORCID

CiênciaID

PRINCIPAL INVESTIGATOR

Gabriela Silva, PhD

ORCID

CiênciaID

PRINCIPAL INVESTIGATOR

Maria do Céu Sousa, PhD

ORCID

CiênciaID

Back

Funded by ERDF - European Regional Development Fund through COMPETE 2020 and National Funds via FCT - Fundação para a Ciência e Tecnologia, under projects POCI-01-0145-FEDER-007440 e UIDB/04539/2020.