Browsing by Author "Figueiredo, Joana"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
- 5-Hydrazinylethylidenepyrimidines effective against multidrug-resistant Acinetobacter baumannii: Synthesis and in vitro biological evaluation of antibacterial, radical scavenging and cytotoxic activitiesPublication . Figueiredo, Joana; Serrano, João L.; Soares, MN; Ferreira, Susana; Domingues, F.C.; Almeida, Paulo; Silvestre, SamuelAcinetobacter baumannii has emerged as an important nosocomial pathogen in recent years, with infectious outbreaks caused by multidrug-resistant strains increasing worldwide. Thus, new antibacterial treatments for multidrug-resistant A. baumannii strains are needed. In this work, a series of 5-hydrazinylethylidenepyrimidines were synthesized and in vitro evaluated against two multidrug-resistant A. baumannii strains (AcB 13/10 and AcB 73/10). Minimum inhibitory concentration results demonstrated that generally the compounds in study presented values in a low micromolar range. In the determination of in vitro bacterial growth at 24 h, it was observed that the pyrimidines 3a and 3c, with an unsubstituted hydrazinylphenyl, have bacteriostatic activity in both multidrug-resistant A. baumannii strains, with a concentration-dependent action. In general, an additive effect occurred in the combination of these compounds with gentamicin, rifampicin and polymyxin B, for both strains. Furthermore, all 5-hydrazinylethylidenepyrimidines under study presented a good 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity, generally low xanthine oxidase inhibition and low cytotoxicity in normal human dermal fibroblasts as well as potential favorable drug-likeness properties. Thus, these molecules can be considered attractive for the future development of antibacterial agents against multidrug-resistant A. baumannii.
- Molecular Beacon Assay Development for Severe Acute Respiratory Syndrome Coronavirus 2 DetectionPublication . Carvalho, Josué; Nunes, J. Lopes; Figueiredo, Joana; Santos, Tiago; Miranda, André; Riscado, Micaela; Sousa, Fani; Duarte, A. P.; Socorro, Sílvia; Tomaz, Cândida; Felgueiras, Mafalda; Teixeira, Rui; Faria, Conceição; Cruz, CarlaThe fast spread of SARS-CoV-2 has led to a global pandemic, calling for fast and accurate assays to allow infection diagnosis and prevention of transmission. We aimed to develop a molecular beacon (MB)-based detection assay for SARS-CoV-2, designed to detect the ORF1ab and S genes, proposing a two-stage COVID-19 testing strategy. The novelty of this work lies in the design and optimization of two MBs for detection of SARS-CoV-2, namely, concentration, fluorescence plateaus of hybridization, reaction temperature and real-time results. We also identify putative G-quadruplex (G4) regions in the genome of SARS-CoV-2. A total of 458 nasopharyngeal and throat swab samples (426 positive and 32 negative) were tested with the MB assay and the fluorescence levels compared with the cycle threshold (Ct) values obtained from a commercial RT-PCR test in terms of test duration, sensitivity, and specificity. Our results show that the samples with higher fluorescence levels correspond to those with low Ct values, suggesting a correlation between viral load and increased MB fluorescence. The proposed assay represents a fast (total duration of 2 h 20 min including amplification and fluorescence reading stages) and simple way of detecting SARS-CoV-2 in clinical samples from the upper respiratory tract.
- Trisubstituted barbiturates and thiobarbiturates: Synthesis and biological evaluation as xanthine oxidase inhibitors, antioxidants, antibacterial and anti-proliferative agentsPublication . Figueiredo, Joana; Serrano, João L.; Cavalheiro, Eunice Cerdeira Soares; Keurulainen, Leena Maria; Yli-Kauhaluoma, Jari Tapani; Moreira, Vânia M; Ferreira, Susana; Domingues, F.C.; Silvestre, Samuel; Almeida, PauloBarbituric and thiobarbituric acid derivatives have become progressively attractive to medicinal chemists due to their wide range of biological activities. Herein, different series of 1,3,5-trisubstituted barbiturates and thiobarbiturates were prepared in moderate to excellent yields and their activity as xanthine oxidase inhibitors, antioxidants, antibacterial agents and as anti-proliferative compounds was evaluated in vitro. Interesting bioactive barbiturates were found namely, 1,3-dimethyl-5-[1-(2-phenylhydrazinyl)ethylidene]pyrimidine-2,4,6(1H,3H,5H)-trione (6c) and 1,3-dimethyl-5-[1-[2-(4-nitrophenyl)hydrazinyl]ethylidene]pyrimidine-2,4,6(1H,3H,5H)-trione (6e), which showed concomitant xanthine oxidase inhibitory effect (IC50 values of 24.3 and 27.9 μM, respectively), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (IC50 values of 18.8 and 23.8 μM, respectively). In addition, 5-[1-(2-phenylhydrazinyl)ethylidene]pyrimidine-2,4,6(1H,3H,5H)-trione (6d) also revealed DPPH radical scavenger effect, with an IC50 value of 20.4 μM. Moreover, relevant cytotoxicity against MCF-7 cells (IC50 = 13.3 μM) was observed with 5-[[(2-chloro-4-nitrophenyl)amino]methylene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione (7d). Finally, different 5-hydrazinylethylidenepyrimidines revealed antibacterial activity against Acinetobacter baumannii (MIC values between 12.5 and 25.0 μM) which paves the way for developing new treatments for infections caused by this Gram-negative coccobacillus bacterium, known to be an opportunistic pathogen in humans with high relevance in multidrug-resistant nosocomial infections. The most promising bioactive barbiturates were studied in silico with emphasis on compliance with the Lipinski's rule of five as well as several pharmacokinetics and toxicity parameters.