The group of Medicinal Chemistry and Drug Discovery aims the discovery of novel small molecules to treat oncologic, neurodegenerative and infectious diseases. The group uses rational drug design, organic and enzymatic synthesis and in vitro biological evaluation to discover novel drug candidates.
A large number of semisynthetic triterpene compounds and oxygenated cholesterol-derivatives has been synthesised and potent antitumor activity has been disclosed for some compounds. Unravelling the biological mechanisms underlying the anticancer properties has been pursued, though not yet completely understood and will require further research. Another approach to find anticancer drugs is from the biological target to the small molecule. Specifically, the active site of PARP-1, an enzyme involved in cancer drug resistance, being an important target by itself in BRCA1- associated cancers, has been explored through structure-based pharmacophore drug design and novel inhibitors have been discovered. Future in vitro biologic and in vivo studies will assess the potential of these molecules to fight cancer.
Alzheimer disease is also a focus of interest in our group. Beta-secretase 1 (BACE-1) has been recognised as an important therapeutic target to fight Alzheimer. A computer-assisted drug discovery approach is being used to discover novel inhibitors of this enzyme. Next steps will be to perform assays to confirm the inhibitory activity. In collaboration with other CNC groups, the inhibitors will be tested using in vivo assays.
Antimicrobial resistance and virulence, host-pathogen interactions, new antimicrobials and therapeutic strategies in microbiology are topics of interest for the group. Loss of antibiotic effectiveness is now a global threat. Our objectives are to characterize resistance mechanisms and molecular epidemiology and find new molecules with potential antimicrobial activity and reduced toxicity.
Group members are: Jorge Salvador (PhD, Group Leader), Alcino Leitão, Andreia Gonçalves, Ana Filipa Salvador, Ana Sofia Valdeira, Bruno Gonçalves, Fátima Nunes, Gabriela Silva, Joana Alves, Joana Velho, Judite Coimbra, Maria do Céu Sousa, Maria de La Salete Baptista, Maria Manuel Silva, Tiago Lima, Vanessa Mendes, Vasco Justino.
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.
Projetos de Desenvolvimento e Implementação de Infraestruturas de Investigação inseridas no RNIE. Rede Nacional de Espectrometria de Massa. Nó da UC (2017-2021). PI: Jorge A. R. Salvador.
Small-molecule inhibitors of human proteasome: a step forward in anticancer drug discovery. FCT - Fundação para a Ciência e Tecnologia (2014-2020). Co-PI: Jorge A. R. Salvador.
Development of an innovative nanosystem to mediate a combined and multi-target therapeutic strategy to hepatocellular carcinoma”. POCI-01-0145-FEDER-30916 (FCT - Foundation for Science and Technology); 2018-2021; PI: Henrique Faneca.