Roberta Jeane Bezerra Jorge

Cumarinas são compostos encontrados na espécie arbórea Platymiscium floribundum, conhecida popularmente como “jacarandá-do-litoral”. Suas propriedades apresentam atividades anti-inflamatórias e antioxidantes. Nesse sentido, o presente estudo objetivou realizar bioprospecção a partir de modificação estrutural da 6,7-dimetoxicumarina (DC) e análise das propriedades físico-químicas e farmacocinéticas de seu derivado reacional 6,7-dimetoxi-3-nitrocoumarina (DNC). As propriedades físico-químicas e o perfil farmacocinético da DNC foram avaliados por meio de plataformas computacionais especializadas, e as análises de acoplamento molecular foram realizadas com o objetivo de predizer a afinidade da DNC com moléculas envolvidas em processos oxidativos e inflamatórios. A análise das propriedades físico-químicas da DNC evidencia um perfil que se enquadra em características típicas de moléculas bioativas. O estudo de acoplamento molecular identificou relevante interação da DNC com moléculas envolvidas em processos antioxidantes e anti-inflamatórios, como heme oxigenase-1 (HO-1) e fator nuclear eritroide 2 (Nrf2). Os resultados do presente estudo indicam que a DNC apresenta propriedades farmacocinéticas compatíveis com desenvolvimento como fármaco de uso sistêmico, sendo recomendadas as avaliações experimentais para validação das predições in silico.

Background: The World Health Organization (WHO) declared a pandemic due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiologic agent responsible for Coronavirus Disease 2019 (COVID-19). Although case numbers declined after the initial outbreak, Brazil experienced slight increases in COVID-19 cases in 2024 and 2025, underscoring the persistent need for effective therapeutic interventions. Recently, proxalutamide—an androgen receptor antagonist—has been proposed as a potential therapeutic agent against COVID-19, as supported by several clinical studies. Methods: In the present work, we aimed to elucidate the molecular interactions between proxalutamide and key proteins involved in the viral fusion and replication processes of SARS-CoV-2. Computational techniques, including molecular docking and molecular dynamics simulations, were employed. Results: Our analyses indicated a high success rate, with stable conformations and favorable binding affinity values for ACE2 (−8.90 kcal/mol) and TMPRSS2 (−9.28 kcal/mol), resulting in strong docking scores. Moreover, molecular dynamics simulations confirmed the stability of these complexes, as evidenced by consistent mean square deviation values, low structural flexibility, a stable radius of gyration, and maintained surface rigidity over a 100 ns simulation period. Conclusions: These combined docking and dynamics results suggest that proxalutamide interacts firmly with the active sites, indicating high binding affinity that may interfere with SARS-CoV-2 entry. Nevertheless, experimental validation and rigorous safety assessments are warranted to confirm this potential.

This study analyzed the effects of a calisthenics-based exercise program on the anthropometric, blood pressure, and functional profiles of hypertensive older women receiving primary health care. Participants were assigned to an intervention group, which performed moderate-intensity calisthenics twice weekly for eight weeks, or a control group, which did not engage in structured exercise. Anthropometric measures, blood pressure, and functional capacity were assessed using the six-minute walk test and the chair stand test. Following the intervention, the intervention group demonstrated a mean increase of 1.32 repetitions in the chair stand test and an average improvement of 78.12 meters in the six-minute walk test, along with reductions in body mass index (−0.57 kg/m2), waist circumference (−0.75 cm), and hip circumference (−1.37 cm), whereas the control group remained stable. These results indicate that the calisthenics program effectively enhanced functional capacity and promoted favorable anthropometric changes in hypertensive older women.

Ruthenium complexes stand out as an excellent alternative in the field of organometallic chemistry with applications in various areas. Recently, in cardiovascular pharmacology, there has been a growing interest in investigating complexes that modulate the Nitric Oxide (NO) pathway without necessarily and directly donating NO. NO has a proven vasodilatory and cardioprotective effect, and it is known that reduced levels are associated with an increased risk of CardioVascular Diseases (CVD). Studies suggest that ruthenium complexes significantly contribute to the treatment of CVD pathophysiology through different pharmacological mechanisms, including the precise delivery of carbon monoxide (CO) to the molecular target, the release of nitric oxide species under visible and invisible (UV) light, the ability to stimulate the activation of soluble Guanylate Cyclase (sGC) enzyme, participation in the opening of potassium channels, and reduction of cytoplasmic calcium levels. This study aims to conduct a narrative review of the cardiovascular effects of ruthenium complexes, focusing on hypertension and myocardial injury, and demonstrate that metal complexes acting on the NO pathway may have promising targets for the development of therapeutic strategies in CVD treatment.

α-Lipoic acid (LA) is an antioxidant of endogenous production, also obtained exogenously. Oxidative stress is closely associated with hypertension, which causes kidney injury and endothelial dysfunction. Here, we evaluated the cardiovascular and renal effects of LA in the two-kidney-one-clip (2K1C) hypertension model. The rats were divided into four groups: Sham surgery (Sham), the two-kidneys-one-clip (2K1C) group, and groups treated with LA for 14 days (Sham-LA and 2K1C-LA). No changes were observed in the pattern of food, water intake, and urinary volume. The left/right kidney weight LKw/RKw ratio was significantly higher in 2K1C animals. LA treatment did not reverse the increase in cardiac mass. In relation to vascular reactivity, there was an increase in the potency of phenylephrine (PHE) curve in the hypertensive animals treated with LA compared to the 2K1C group and also compared to the Sham group. Vasorelaxation induced by acetylcholine (Ach) and sodium nitroprusside (SNP) were not improved by treatment with LA. Urea and creatinine levels were not altered by the LA treatment. In conclusion, the morphological changes in the aorta and heart were not reversed; however, the treatment with LA mitigated the contraction increase induced by the 2K1C hypertension.

In Brazil, around 80% of snakebites are caused by snakes of the genus Bothrops. A three-dimensional culture model was standardized and used to perform treatments with Bothrops erythromelas venom (BeV) and its antivenom (AV). The MRC-5 and L929 cell lines were cultured at increasing cell densities. Morphometric parameters were evaluated through images obtained from an inverted microscope: solidity, circularity, and Feret diameter. L929 microtissues (MT) showed better morphometric data, and thus they were used for further analysis. MT viability was assessed using the acridine orange and ethidium bromide staining method, which showed viable cells in the MT on days 5, 7, and 10 of cultivation. Histochemical and histological analyses were performed, including hematoxylin/eosin staining, which showed a good structure of the spheroids. Alcian blue staining revealed the presence of acid proteoglycans. Immunohistochemical analysis with ki-67 showed different patterns of cell proliferation. The MT were also subjected to pharmacological tests using the BeV, in the presence or absence of its AV. The results showed that the venom was not cytotoxic, but it caused morphological changes. The MT showed cell detachment, losing their structure. The antivenom was able to partially prevent the venom activities.

Nitrosyl ruthenium complexes have emerged as promising platforms for the controlled delivery of nitric oxide (NO) and nitroxyl (HNO), both of which possess significant therapeutic implications. Considering this scenario, we synthesized and characterized the metal complex cis‐[RuNO(phen)₂(2MIM)]³⁺ and its precursors, where phen and 2MIM correspond to 1,10‐phenantroline and 2‐methylimidazole, respectively. Comprehensive structural elucidation was undertaken using a combination of spectroscopic and electrochemical methodologies, including XANES/EXAFS experiments. This structural data was further validated through DFT computational analyses. We demonstrated that such compound can release NO and HNO in the presence of thiol‐based substrates. Not only this, but the same metal complex can also delivery nitric oxide under irradiation with visible light (λ=460 nm). The nitrosyl complex and its derivatives displayed marked vasodilatory capabilities as evidenced in assays involving isolated rat aorta rings. They also exhibited commendable antioxidant activity in free radical scavenging assays. Collectively, based on these data, this nitrosyl ruthenium compound is a potential therapeutic candidate, especially in the field of cardiovascular pathology like atherosclerosis, thereby deserving further in‐depth investigations.