A5071697320- Synthesis and bioactivity of alkaloids
- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- Cancer therapeutics and mechanisms
- RNA Interference and Gene Delivery
- Synthesis and pharmacology of benzodiazepine derivatives
- Phenothiazines and Benzothiazines Synthesis and Activities
- Synthesis and Reactivity of Heterocycles
- Synthesis and Biological Evaluation
- Radiopharmaceutical Chemistry and Applications
- Mercury impact and mitigation studies
- Cancer Treatment and Pharmacology
- Malaria Research and Control
- Click Chemistry and Applications
- Marine animal studies overview
- Radiation Therapy and Dosimetry
- Heavy metals in environment
- Chemotherapy-related skin toxicity
- Chemical synthesis and alkaloids
- Monoclonal and Polyclonal Antibodies Research
- Electron and X-Ray Spectroscopy Techniques
- Radioactivity and Radon Measurements
- HIV/AIDS drug development and treatment
- Research on Leishmaniasis Studies
- Metal complexes synthesis and properties
University of Lisbon
2010-2023
Instituto Politécnico de Lisboa
2017
Instituto de Investigacao das Pescas e do Mar
2004-2008
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...
Abstract A new family of 99m Tc(I)- tricarbonyl complexes and 125 I-heteroaromatic compounds bearing an acridine orange (AO) DNA targeting unit was evaluated for Auger therapy. Characterization the interaction, performed with non-radioactive Re 127 I congeners, confirmed that all act as intercalators. Both classes induce double strand breaks (DSB) in plasmid but extent damage is strongly dependent on linker between emitter ( Tc or I) AO moiety. The vitro evaluation complemented molecular...
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...
Indole alkaloids ellipticine (1), cryptolepine triflate (2a), rationally designed 11-(4-piperidinamino)cryptolepine hydrogen dichloride (2b) and olivacine (3) (an isomer of 1) were evaluated in vitro against Plasmodium falciparum vivo berghei-infected mice. 1-3 inhibited P. (IC₅₀≤1.4 μM, order activity: 2b>1>2a>3). In toxicity to murine macrophages was revealed selectivity indices (SI) 10-12 for 2a SI>2.8×10² 1, 2b 3. 1 administered orally at 50mg/kg/day highly active berghei (in inhibition...
A guanine-rich strand within the promoter of KRAS gene can fold into an intra-molecular G-quadruplex structure (G4), which has important role in regulation transcription. We have previously identified indolo[3,2-b]quinolines with a 7-carboxylate group and three alkylamine side chains (IQ3A) as effective G4 stabilizers promising selective anticancer leads. Herein we investigated mechanism action these compounds, hypothesized due to stabilization sequence subsequent down-regulation...
Abstract G‐quadruplex (G4) DNA structures in telomeres and oncogenic promoter regions are potential targets for cancer therapy, G4 ligands have been shown to modulate telomerase activity oncogene transcription. Herein we report the synthesis thermal stabilisation effects, determined by FRET melting assays, of 20 indolo[3,2‐ b ]quinolines mono‐, di‐, trisubstituted with basic side chains. Molecular modelling studies were also performed an attempt rationalise ligands′ binding poses G4....
Abstract A library of 5‐methylindolo[3,2‐ c ]quinolones (IQc) with various substitution patterns alkyldiamine side chains were evaluated for G‐quadruplex (G4) binding mode and efficiency. Fluorescence resonance energy transfer melting assays showed that IQcs a positive charge in the heteroaromatic nucleus two weakly basic are potent selective human telomeric (HT) gene promoter G4 stabilizers. Spectroscopic studies HT as model an IQc stabilizing complex involves molecules...
To get insight into the relevance of targeting hemozoin (Hz) crystals, two isomeric series, N5,N10-bis-alkylamine (2a-k) and N10,O11-bis-alkylamine (3a-k) indolo[3,2-b]quinolines, were evaluated for their in vitro activity against chloroquine (CQ)-resistant sensitive strains Plasmodium falciparum. In general, compounds series 3 more active than isomers 2, with IC50/LD50 ranging from 25/233 nM (3i) to 1.3 (3a)/10.7 (3b) μM. SAR analyses showed that lipophilicity chlorine substitution at C3...
Quadruplex nucleic acids are promising targets for cancer therapy. In this study we used a fragment-based approach to create new flexible G-quadruplex (G4) DNA-interactive small molecules with good calculated oral drug-like properties, based on quinoline and triazole heterocycles. G4 melting temperature polymerase chain reaction (PCR)-stop assays showed that two of these compounds selective ligands, as they were able induce stabilize G4s in dose- DNA sequence-dependent manner. Molecular...
Quindoline (QUIND, indolo[3,2-b]quinoline) and cryptolepine (CRYPT, 5-methyl-10H-indolo[3,2-b]quinoline) together with their corresponding derivatives have been studied for decades due to important biological activity against diseases like malaria. The of drugs is routinely investigated using fluorescence based methods. However, recent reports show that the photophysics CRYPT its analogues not yet understood. Herein, QUIND in aqueous solutions at different pH values both protic aprotic...
Knowledge of protonable sites and acid dissociation constants cryptolepine derivatives having C‐11 substituents containing two amino functionalities is great importance to the understanding mechanism their antimalarial action, which may contribute further development as drug candidates. In this work, we applied 1 H NMR titration investigate acid–base characteristics these polyprotic compounds in pH range 3–13. We identified three equilibria with most (p K a *) being greater than 10.5,...
Abstract The synthesized compounds, especially compounds (IIIb) and (IVb) show high G‐Quadruplex (G4) thermal stabilization over duplex DNA selectivity for the HCT116 cancer cell line primary rat hepatocytes.