Síntese e avaliação de potencial atividade antitumoral de derivados arilfuranos / Synthesis and evaluation of potential antitumor activity of arylfuran derivatives

Fármacos que possuem um anel furano em sua estrutura são versáteis quanto à sua atividade biológica, sendo utilizados para diversas funções terapêuticas, como antitumoral. O câncer é, atualmente, um dos principais problemas de saúde pública mundial, estando entre as quatro principais causas de morte prematura na maioria dos países. No presente trabalho, oito derivados arilfuranos foram sintetizados e testados frente a linhagens de células tumorais de mama (MCF7) e leucemia mielóide (K562). Desses, alguns demonstraram valores de IC50 bastante promissores, como (3) (30,55 μM ± 1,78 para MCF7 e 41,68 ± 2,33 para K562), (5) (29,20 μM ± 1,10 para K562), (6) (32,50 ± 2,50 para K562) e (10) (30,46 μM ± 2,52 para MCF7 e 28,98 μM ± 1,84 para K562)

Correction: de Almeida et al. Acute Promyelocytic Leukemia (APL): A Review of the Classic and Emerging Target Therapies towards Molecular Heterogeneity. <i>Future Pharmacol.</i> 2023, <i>3</i>, 162–179

In the original publication [...

Influence of ACE I/D Polymorphism on Circulating Levels of Plasminogen Activator Inhibitor 1, D-Dimer, Ultrasensitive C-Reactive Protein and Transforming Growth Factor β1 in Patients Undergoing Hemodialysis.

BACKGROUND:There is substantial evidence that chronic renal and cardiovascular diseases are associated with coagulation disorders, endothelial dysfunction, inflammation and fibrosis. Angiotensin-Converting Enzyme Insertion/Deletion polymorphism (ACE I/D polymorphism) has also be linked to cardiovascular diseases. Therefore, this study aimed to compare plasma levels of ultrassensible C-reactive protein (usCRP), PAI-1, D-dimer and TGF-β1 in patients undergoing HD with different ACE I/D polymorphisms. METHODS:The study was performed in 138 patients at ESRD under hemodialysis therapy for more than six months. The patients were divided into three groups according to the genotype. Genomic DNA was extracted from blood cells (leukocytes). ACE I/D polymorphism was investigated by single polymerase chain reaction (PCR). Plasma levels of D-dimer, PAI-1 and TGF-β1 were measured by enzyme-linked immunosorbent assay (ELISA), and the determination of plasma levels of usCRP was performed by immunonephelometry. Data were analyzed by the software SigmaStat 2.03. RESULTS:Clinical characteristics were similar in patients with these three ACE I/D polymorphisms, except for interdialytic weight gain. I allele could be associated with higher interdialytic weight gain (P = 0.017). Patients genotyped as DD and as ID had significantly higher levels of PAI-1 than those with II genotype. Other laboratory parameters did not significantly differ among the three subgroups (P = 0.033). Despite not reaching statistical significance, plasma levels of usCRP were higher in patients carrying the D allele. CONCLUSION:ACE I/D polymorphisms could be associated with changes in the regulation of sodium, fibrinolytic system, and possibly, inflammation. Our data showed that high levels of PAI-1 are detected when D allele is present, whereas greater interdialytic gain is associated with the presence of I allele. However, further studies with different experimental designs are necessary to elucidate the mechanisms involved in these associations

Association among ACE, ESR1 polymorphisms and preeclampsia in Brazilian pregnant women.

Background: Genetic, immune and environmental factors are involved in preeclampsia (PE) etiopathogenesis. Considering that hypertension and poor placental perfusion are important features in PE, polymorphisms in the angiotensin-converting enzyme (ACE) and estrogen nuclear receptor 1 (ESR1) genes could be involved in the predisposition and/or development of the disease. The aim of this study was to evaluate if polymorphisms in ACE and ESR1 genes were associated with PE occurrence. Material and Methods: This case-control study included 209 Brazilian pregnant women (107 with severe PE and 102 normotensive controls). The polymorphisms were investigated by polymerase chain reaction (PCR) followed by polyacrylamide gel electrophoresis. Results: No significant difference between PE versus normotensive pregnant women, as well as early versus late PE, was observed when compared the allelic and genotypic frequencies of insertion/deletion polymorphism in intron 16 of the ACE gene and the single nucleotide polymorphisms (SNPs - rs2234693 and rs9340799) of the ESR1 gene. Conclusion: This pioneer study involving Brazilian women showed no association among the studied polymorphisms and PE, which suggests that ins/del ACE and SNPs ESR1 do not contribute to this disease occurrence in Brazil

Circulating microparticles and thrombin generation in patients with Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukemia (CLL) has shown great biological heterogeneity, with a variable prognosis, and a short survival in some patients. In this light, the present study focused on the prognostic utility of circulating microparticles (MPs) and a Thrombin Generation (TG) Profile for thrombotic risk and disease progression in CLL patients. Circulating microparticles and TG were evaluated in 35 patients with CLL and 35 healthy individuals. For circulating microparticles, significant differences were observed among the following groups: MPs derived from endothelial cells (p&nbsp;= 0.002), B lymphocytes (p&nbsp;&lt; 0.001), platelets (p&nbsp;= 0.003), and Tissue Factor MPs in monocytes (p&nbsp;&lt; 0.001). In all cases, MP values were higher for the CLL group. When compared to the controls, CLL patients presented a decrease in TG, characterized by a reduced endogen thrombin potential (ETP) (p&nbsp;= 0.031). When the results were analyzed according to the Binet stage, as compared to the controls, the Binet B+C group also presented lower ETP values (p&nbsp;= 0.009). No significant differences were observed between the control and the Binet A groups or between the Binet A and the Binet B + C groups. Although hemostatic alterations may occur in patients with CLL, these parameters do not seem to be useful to indicate disease progression

Clinical and epidemiological characteristics of studied patients in different genotype groups for ACE I/D polymorphism.

<p>Clinical and epidemiological characteristics of studied patients in different genotype groups for ACE I/D polymorphism.</p

Electrophoresis on polyacrylamide gel stained with silver nitrate of PCR products to identify ACE polymorphism.

<p>Molecular weight standard of 50 bp; 3: DNA from individual homozygous II (599 bp); 4: DNA from individual heterozygous ID (599 and 312 bp); 5: DNA from individual homozygous DD (312 bp); 6: negative control.</p

Distribution of PAI-1 (ng / mL) plasma levels in groups DD, ID and II.

<p>The horizontal lines indicate the medians obtained.</p