DSpace Coleção: PPGDITM

Desenvolvimento e caracterização de um modelo de senescência induzida por D-galactose e avaliação dos efeitos do alfa-terpineol em embriões e larvas de zebrafish (Danio rerio)

2026-10-09T06:12:00Z

Título: Desenvolvimento e caracterização de um modelo de senescência induzida por D-galactose e avaliação dos efeitos do alfa-terpineol em embriões e larvas de zebrafish (Danio rerio) Autor(es): Menezes, Geovânia Maria Sales de Orientador: Medeiros, Isac Almeida de Abstract: Cellular senescence, a fundamental mechanism of aging, is implicated in several cardiovascular diseases. The zebrafish model (Danio rerio) is a well-established gerontological model; however, D-galactose (D-gal)–induced aging has not yet been tested in zebrafish larvae. The aim of this study was to select, through in silico screening, compounds present in five fruits from Northeastern Brazil with the highest activity in enzymatic pathways involved in aging- associated cardiovascular diseases, as well as to develop in vivo a D-galactose–induced senescence model and to evaluate the effects of α-terpineol(α-T) on senescence, oxidative stress, and heart rate in zebrafish embryos and larvae. Sixty-seven compounds from typical fruits of Northeastern Brazil were investigated in silico for activity in pathways associated with aging-related cardiovascular disease (NRF2, iNOS, NOX, and COX2). Model performance, proComb and Pact docking activity, and molecular docking and molecular dynamics were evaluated. In studies with D. rerio embryos (n = 100), acute toxicity of α-terpineol (OECD 236), mortality rate, and D-gal–induced morphological alterations were assessed. Subsequently, embryos (n = 60) were treated for six days to evaluate morphological changes induced by D- gal (36.03 mg/mL) and the effects of α-terpineol at concentrations of 0.00046 mg/mL and 0.0046 mg/mL.A senescence model was then developed by exposing zebrafish embryos and larvae to D-gal for 72 hours, divided into the following groups: Control (E3 medium); D- galactose (30 mg/mL); D-gal + low-dose α-terpineol (0.000047 mg/mL); D-gal + high-dose α- terpineol (0.000094 mg/mL); and D-gal + resveratrol (RSV, 0.01 mg/mL). Senescence (n = 15), oxidative stress assessed by catalase activity (n = 50), survival and morphological alterations (n = 100), and heart rate (n = 50) were evaluated in the larvae. Student’s t-test and one-way ANOVA followed by Bonferroni post hoc tests were used for statistical analysis. In silico results revealed four robust enzymatic models, with 48 active compounds targeting two or more enzymes; among these, 16 showed activity ≥ 0.6 for NRF2 and ≥ 0.5 for at least one additional enzyme. α-Terpineol was selected for in vivo assays due to its superior molecular dynamics performance, indicating greater stability. The LC₅₀ values for α-terpineol and D-gal were above 0.1 mg/mL and 45.03 mg/mL, respectively, and the LOAEL for α-terpineol was 0.0062 mg/mL. Initial tests with D-gal + α-terpineol (0.0046 and 0.00046 mg/mL) did not reduce the percentage of morphological alterations compared with the E3 group (p < 0.05), but attenuated the severity of the alterations.The developed D-gal–induced senescence model in zebrafish embryos and larvae resulted in a high survival rate (95%), increased β-galactosidase activity in the D-gal group, and reduced activity in the D-gal + low-dose α-terpineol group (p < 0.05). Catalase activity increased and heart rate decreased in the D-gal–treated groups (p < 0.05) compared with the control; however, α-terpineol treatment was not effective in attenuating these effects. In conclusion, novel compounds exhibited activity in aging-associated cardiovascular pathways, particularly those related to NRF2, with α-terpineol standing out. The D-gal–induced senescence model proved to be functional, as demonstrated by increased β-galactosidase levels, elevated catalase activity, and altered heart rate, and low-dose α-terpineol was able to attenuate senescence. Therefore, the use of the developed model is suggested for future studies, along with further molecular and functional approaches to deepen mechanistic understanding of α- terpineol’s effects. Editor: Universidade Federal da Paraíba Tipo: Tese

Estudo da atividade antifúngica do (R)-(+)-limoneno contra cepas de Candida glabrata

2026-10-06T06:12:11Z

Título: Estudo da atividade antifúngica do (R)-(+)-limoneno contra cepas de Candida glabrata Autor(es): Pires, Bruna Araujo Orientador: Oliveira Filho, Abrahão Alves de Abstract: Fungal infections of the genus Candida are among the most common in the world and, consequently, resistance to existing antifungal agents is a very challenging reality. In this sense, medicinal plant-based substances can aid in the design of pharmacologically important products and contribute to the development of innovative therapeutic alternatives. Given this, the objective of this study was to investigate the antifungal potential of the monoterpene (R)-(+)-limonene against strains of Candida glabrata (Nakaseomyces glabrata). Antifungal activity was determined by the broth microdilution technique for the minimum inhibitory concentration (MIC) and, subsequently, the minimum fungicidal concentration (MFC) was determined. Next, the association test was performed using the checkerboard technique. The mechanism of action of the possible antifungal activity was analyzed by sorbitol and ergosterol assays. Molecular docking was also performed to evaluate the molecular interactions of (R)-(+)-Limonene with the enzyme 1,3-β-glucanase and sterol 14α-demethylase. Based on the tests, (R)-(+)-Limonene presented a MIC and MFC of 256 μg/mL, with fungicidal characteristics, showing strong inhibitory activity for strains ATCC 9003, LM 13, and LM 16 and moderate activity for LM 46. The mechanism of action involves both the cell wall and the fungal plasma membrane. In addition, the molecular docking study pointed to an interaction between (R)-(+)-Limonene and the active sites of the proteins 1,3-β-glucanase and sterol 14α-demethylase (CYP51), the latter being more robust. As for the association test, the antifungal potential of (R)-(+)-Limonene was demonstrated when used individually, without association with fluconazole. Based on these findings, it can be concluded that (R)-(+)-Limonene is a very promising monoterpene for the development of new drugs for the treatment of candidiasis caused by Candida glabrata (Nakaseomyces glabrata). Editor: Universidade Federal da Paraíba Tipo: Tese

Desenvolvimento de um compósito fotopolimerizável para alongamento, recuperação e tratamento das unhas

2026-10-01T06:10:30Z

Título: Desenvolvimento de um compósito fotopolimerizável para alongamento, recuperação e tratamento das unhas Autor(es): Sousa, Ivancia Donato de Luna Orientador: Diniz, Margareth de Fátima Formiga Melo Abstract: The search for photopolymerizable formulations that are both safe and functionally compatible with the nail plate has gained increasing attention due to the limitations of commercial composites, which are often associated with structural damage, reduced mechanical resistance, and increased susceptibility to onychomycosis. In this study, an innovative photopolymerizable composite was developed, containing an optimized organic matrix and micronized inorganic salts capable of interacting with keratin, aiming to promote nail extension, recovery, and treatment. The formulation was subjected to comprehensive physicochemical characterization, including scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and ultraviolet–visible spectroscopy (UV–Vis), enabling the selection of the system with improved thermal stability, reduced degradation prior to curing, and an optical profile favorable to photopolymerization. Complementary assays using human nail plates demonstrated adequate adhesion, absence of infiltration, and formation of a continuous film. Non-clinical toxicological evaluation using Caenorhabditis elegans included hatching and motility assays, in which the photopolymerizable matrix showed low toxicity limited to these endpoints, with no lethal effects or relevant behavioral alterations. These findings support a preliminary safety profile for topical use. Finally, the safety and performance of the composite were evaluated in a Phase I clinical study with volunteers using standardized image acquisition and instrumental metrics. The results showed progressive improvement in gloss, texture, perceived thickness, and surface integrity, as well as the absence of product-related adverse reactions. Overall, the findings indicate that the developed composite presents favorable safety and clinical applicability, representing a technologically advanced alternative to conventional systems used for nail extensions and ungual therapies. This study contributes to the scientific and regulatory advancement of photopolymers intended for nail care, opening perspectives for subsequent studies on expanded efficacy and new dermocosmetic applications. Editor: Universidade Federal da Paraíba Tipo: Tese

Síntese e avaliação farmacocinética in silico de compostos híbridos com potencial bioativo: chalconas quinolínicas e derivados heterocíclicos do ácido salicílico

2026-09-10T06:12:15Z

Título: Síntese e avaliação farmacocinética in silico de compostos híbridos com potencial bioativo: chalconas quinolínicas e derivados heterocíclicos do ácido salicílico Autor(es): Duarte, Gabrielly Diniz Orientador: Rodrigues, Luis Cezar Abstract: The growing demand for therapeutics with higher efficacy and lower toxicity has driven the development of innovative synthetic strategies in medicinal chemistry. In this context, molecular hybridization emerges as a promising approach, enabling the design of compounds that combine different pharmacophoric nuclei into a single structure, thereby expanding their bioactive potential. This study aimed to perform the rational design, synthesis, and in silico pharmacokinetic evaluation of novel hybrid molecules belonging to the classes of quinoline-based chalcones and heterocyclic derivatives of salicylic acid. Chalcones, traditionally known for their broad spectrum of biological activities (antitumor, antibacterial, and anti-inflammatory), yet limited by intrinsic pharmacokinetic drawbacks (poor water solubility, low bioavailability, and potential toxicity), were functionalized with the quinoline scaffold, recognized for improving physicochemical properties such as lipophilicity and metabolic stability. In parallel, salicylic acid, due to its versatile bioactivity, was modified through halogenation and cyclization strategies, yielding unprecedented structures. The methodology involved classical organic synthesis routes, including Claisen-Schmidt condensations and nucleophilic substitutions, as well as computational predictions using the Deep-PK server to assess pharmacokinetic parameters. Five compounds were synthesized: the intermediate 4-((7-chloroquinolin-4-yl)oxy)-3- methoxybenzaldehyde (GAD1), two chalcone derivatives of GAD1 (GAD2 and GAD3), a cyclic salicylic acid dimer (GAD4), and a brominated heterocyclic derivative (GAD5), all obtained with yields above 75% through precipitation. In silico analyses suggested favorable pharmacokinetic profiles, particularly for the quinoline-chalcones GAD2 and GAD3, which exhibited predicted good intestinal absorption, low hepatotoxicity, and reduced CYP450 isoform inhibition compared with their non-quinoline analogues. Similarly, GAD4 and GAD5 demonstrated trends toward improved metabolic stability and toxicity parameters relative to salicylic acid. Despite the inherent limitations of computational predictions, the findings highlight the feasibility of these structural modifications as a starting point for future in vitro and in vivo investigations. Editor: Universidade Federal da Paraíba Tipo: Tese