A5051777092- Malaria Research and Control
- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Computational Drug Discovery Methods
- Synthesis and biological activity
- Synthesis and Catalytic Reactions
- HIV/AIDS drug development and treatment
- Synthesis and Biological Evaluation
- Cancer therapeutics and mechanisms
- Peptidase Inhibition and Analysis
- Phenothiazines and Benzothiazines Synthesis and Activities
- Chemical Reaction Mechanisms
- Synthesis of β-Lactam Compounds
- Bioactive Compounds and Antitumor Agents
- Drug Transport and Resistance Mechanisms
- Synthesis and bioactivity of alkaloids
- Research on Leishmaniasis Studies
- Advanced biosensing and bioanalysis techniques
- Synthesis and Characterization of Heterocyclic Compounds
- Protease and Inhibitor Mechanisms
- Crystallization and Solubility Studies
- Pneumocystis jirovecii pneumonia detection and treatment
- RNA Interference and Gene Delivery
- X-ray Diffraction in Crystallography
- Chemical Reactions and Mechanisms
University of Lisbon
2016-2025
Centro Hospitalar do Baixo Vouga
2016-2023
Universidade Nova de Lisboa
2023
Universidade do Porto
2004-2020
Centro Hospitalar do Porto
2017-2019
Hospitais da Universidade de Coimbra
2019
Universidade Federal de Viçosa
2018
Hospital of St. Francis Xavier
2015
Instituto Politécnico de Lisboa
2015
Université Paris 8
2013
Leucine-rich repeat kinase 2 (LRRK2) is one of the most promising targets for Parkinson's disease. LRRK2-targeting strategies have primarily focused on type 1 inhibitors, which, however, limitations as inhibited protein can interfere with natural mechanisms, which could lead to undesirable side effects. Herein, we report development LRRK2 proteolysis targeting chimeras (PROTACs), culminating in discovery degrader XL01126, an alternative strategy. Initial designs and screens PROTACs based...
Plasmodium parasites undergo a clinically silent and obligatory developmental phase in the host’s liver cells before they are able to infect erythrocytes cause malaria symptoms. To overcome scarcity of compounds targeting stage malaria, we screened library 1037 existing drugs for their ability inhibit hepatic development. Decoquinate emerged as strongest inhibitor stages, both vitro vivo. Furthermore, decoquinate kills parasite’s replicative blood stages is active against developing...
Residence within a customized vacuole is highly successful strategy used by diverse intracellular microorganisms. The parasitophorous membrane (PVM) the critical interface between Plasmodium parasites and their possibly hostile, yet ultimately sustaining, host cell environment. We show that torins, developed as ATP-competitive mammalian target of rapamycin (mTOR) kinase inhibitors, are fast-acting antiplasmodial compounds unexpectedly parasite directly, blocking dynamic trafficking proteins...
Abstract KRAS is one of the most frequently mutated oncogenes in human cancer, yet remaining undruggable. To explore a new therapeutic strategy, library 5-methyl-indolo[3,2-c]quinoline derivatives (IQc) with range alkyldiamine side chains was designed to target DNA and RNA G-quadruplexes (G4) promoter 5′-UTR mRNA gene. Biophysical experiments showed that di-substituted IQc compounds are potent selective G4 stabilizers. They preferentially inhibit proliferation mutant cancer cell lines (0.22...
It is widely accepted that the struggle against malaria depends on development of new strategies to fight infection. The "magic bullet" thought be necessary reach eradication should not only provide treatment for all Plasmodium spp. infect human red blood cells but also eliminate replicative and dormant liver forms parasite. Moreover, these goals ideally achieved by using different mechanisms action so as avoid resistance. To end, two hybrid molecules with covalently linked primaquine...
The synthesis of cryptolepine derivatives containing basic side-chains at the C-11 position and their evaluations for antiplasmodial cytotoxicity properties are reported. Propyl, butyl, cycloalkyl diamine side chains significantly increased activity against chloroquine-resistant Plasmodium falciparum strains while reducing when compared with parent compound. Localization studies inside parasite blood stages by fluorescence microscopy showed that these accumulate nucleus, indicating...
The use of artemisinin or other endoperoxides in combination with drugs is a strategy to prevent development resistant strains Plasmodium parasites. Our previous work demonstrated that hybrid compounds, comprising and vinyl sulfones, were capable high activity profiles comparable chloroquine while acting through two distinct mechanisms action: oxidative stress falcipain inhibition. In this study, we adapted approach novel class inhibitors: peptidomimetic pyrimidine nitriles. Pyrimidine...
Boronic acids (BAs) are a prominent functionality extensively used to design biologically active compounds and functional biomaterials. open shell can lead unspecific reactivity of BAs with endogenous nucleophiles undesired off-target effects. Here, diazaborines presented as new class boron-based warheads for serine proteases inhibition, in which the boron function is stabilized form an aromatic heterocycle. In this study, were readily synthesized single step yields up 96%, without any...
Accumulation of mutated superoxide dismutase 1 (mSOD1) in amyotrophic lateral sclerosis (ALS) involves injury to motor neurons (MNs), activation glial cells and immune unbalance. However, neuroinflammation, besides its detrimental effects, also plays beneficial roles ALS pathophysiology. Therefore, the targeting microglia modulate release inflammatory neurotoxic mediators their exosomal dissemination, while strengthening cell neuroprotective properties, has gained growing interest. We used...
Reactive astrocytes in Amyotrophic Lateral Sclerosis (ALS) change their molecular expression pattern and release toxic factors that contribute to neurodegeneration microglial activation. We others identified a dysregulated inflammatory miRNA profile ALS patients mice models suggesting they represent potential targets for therapeutic intervention. Such cellular miRNAs are known be released into the secretome carried by small extracellular vesicles (sEVs), which may harmful recipient cells....
Imidazolidin-4-one derivatives of primaquine were synthesized as potential double prodrugs the parent drug. The title compounds inhibit development sporogonic cycle Plasmodium berghei, affecting appearance oocysts in midguts mosquitoes. imidazolidin-4-ones are very stable, both human plasma and pH 7.4 buffer, indicating that they active per se. Thus, derived from 8-aminoquinolines represent a new entry antimalarial structure−activity relationships.