https://repositorio.ufpb.br/jspui/handle/tede/8251 PPGDITM 2026-04-08T01:15:30Z https://repositorio.ufpb.br/jspui/handle/123456789/37816 Título: Avaliação do potencial antimicobacteriano da Caulerpina e seus derivados em modelos in silico e in vitro Autor(es): Oliveira, Ana Caroline Melo de Queiroz Orientador: Santos, Bárbara Viviana de Oliveira Abstract: Human tuberculosis (TB) is an infectious disease caused mainly by Mycobacterium tuberculosis (Mtb), a pathogenic, micro-aerophilic bacterium that commonly affects the lungs and is one of the most infectious diseases in the world. Due to the emergence of resistant bacterial strains, TB is still a particularly challenging disease, a fact attributed mainly to poor adherence to treatment protocols, spontaneous mutations in the genome of these microorganisms, and drug side effects. Thus, continuous efforts are needed for the discovery and development of new anti-TB drugs. The marine environment is a valuable source of diverse natural products. The chemical diversity of its molecules has provided the discovery of many novel products, among them caulerpine, the major substance of the species Caulerpa racemosa, a bis-indolic alkaloid, with proven antioxidant, antifungal, antispasmodic, antinociceptive, anti-inflammatory, antiviral, and leishimanicidal biological activity. According to the pharmacological potential of this molecule, studies have been conducted to develop analogues by the introduction of new substituents, which resulted in significant chemical differences and different pharmacokinetic properties. The present work aimed to synthesize and evaluate the antimycobacterial potential of PLC and its derivatives in Mtb models, through in silico and in vitro studies, as an initial step towards the development of prototype drug candidates for TB treatment. Therefore, molecular modeling studies were performed using Mtb target proteins and as ligands the indolic alkaloid CLP and its analogues, with the construction of a predictive model using in silico methodologies, followed by the isolation of CLP, synthesis of derivatives with different substituents in the ester function. In vitro tests were performed to determine the susceptibility of mycobacteria to the compounds by determining the minimum inhibitory concentration (MIC) of those with higher activity in Mtb culture and in silico evaluation of oral bioavailability and absorption, distribution, excretion and toxicity (ADMET) properties. The molecular docking study of synthetic CLP derivatives of the four proteins analyzed (DpE1, Pantothenate synthetase, Enoil-ACP reductase and Dihydrofolate reductase) showed that the synthetic CLP derivatives obtained negative energies in all enzymes under study, thus revealing that interaction occurred with all targets, highlighting the diisobutyl CLP, which showed greater affinity in the Pantothenate synthetase target. The in vitro evaluation of the most promising molecules was carried out, aiming to determine the susceptibility of mycobacteria to the compounds, finding that the diisobutyl CLP analog showed the most promising results (=125 μM). In the in silico evaluation for determination of theoretical oral bioavailability parameters, seven analogues showed promising pharmacokinetic activities and, with regard to the evaluation of theoretical ADMET, most showed good results. Editor: Universidade Federal da Paraíba Tipo: Tese 2023-07-10T00:00:00Z https://repositorio.ufpb.br/jspui/handle/123456789/37715 Título: Avaliação da atividade antibacteriana do óleo essencial, nanoemulsão e nanoemulgel de Eucalyptus staigeriana sobre cepas de Klebsiella pneumoniae Autor(es): Paula, Andrea Fernanda Ramos de Orientador: Oliveira Filho, Abrahão Alves de Abstract: Infections caused by multidrug-resistant microorganisms, such as Klebsiella pneumoniae, are a threat to public health due to their complex genetic mechanisms. In this context, essential oils of Eucalyptus staigeriana have promising antibacterial properties, however, their efficacy against Gram-negative strains is limited. Faced with this challenge, innovative drug delivery systems, such as nanoemulsions and nanoemulgels, can improve the stability and efficacy of these oils, which highlights the need for more research to confirm their potential. In this sense, the general objective of the study was to evaluate the antibacterial activities of the essential oil, nanoemulsion and nanoemulgel of Eucalyptus staigeriana against strains of Klebsiella pneumoniae, encompassing the obtention, development, and characterization of the nanostructured systems.For the essential oil, chromatographic analysis was performed and the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were determined by microdilution in plates, and the Minimum Adhesion Inhibitory Concentration (CIMA) by test tubes. The association of the essential oil with antibacterials was evaluated by diffusion in solid medium. For the emulsified systems, the value of the Hydrophilic-Lipophilic Equilibrium (EHL) was determined for the emulsification of the essential oil. The nanoemulsions were produced by ultrasonication, using essential oil, surfactants (Span® 80 + Tween® 80) and ultrapure water, and analyzed for organoleptic and physicochemical characteristics. Mean droplet size and polydispersion index (PDI) were determined using Zetasizer Ultra Red. The best formulation was selected and its stability evaluated from D1 to D90. The nanoemulgel was prepared by incorporating the nanoemulsion into a gel base with 1% carbopol, following the same evaluation criteria as nanoemulsions for characterization and stability. The antibacterial activity of the nanoemulsion was evaluated by MIC and CBM, while the nanoemulgel was tested by diffusion on well agar. The essential oil of Eucalyptus staigeriana showed strong antibacterial activity with MIC of 500μg/mL and MBC greater than 1000 mg/mL, demonstrating bacteriostatic effect. In addition to greater non-stick activity in a ratio of 1:2 compared to chlorhexidine digluconate. When combined with ciprofloxacin, a more pronounced synergistic effect was observed. The main components of the essential oil were: sylvan (40.81%), geraniol (13.45%), nerol (9.53%), terpinolene (5.75%) and methyl geranate (6.16%). The optimized nanoemulsion (15% oil, 10% surfactants and 75% water, EHL12) showed satisfactory physicochemical and organoleptic properties, with lower PDI (0.19) and mean droplet diameter ≤ 100 nm (94.29 nm), maintaining the antibacterial activity. Both the nanoemulsion and the nanoemulgel remained stable for up to 90 days, and the nanoemulgel also demonstrated antibacterial efficacy against the same strains. It is concluded that the essential oil of Eucalyptus staigeriana and the formulations of nanoemulsion and nanoemulgel, have effective antimicrobial action against Klebsiella pneumoniae, showing promise for the development of new pharmaceutical products. Editor: Universidade Federal da Paraíba Tipo: Tese 2025-07-28T00:00:00Z https://repositorio.ufpb.br/jspui/handle/123456789/37563 Título: Caracterização físico-química e avaliação dos efeitos antibacteriano, antioxidantes e citotóxicos do exsudato de Anacardium occidentale L. (goma do cajueiro): um possível tratamento para mucosite oral Autor(es): Limeira, Rebecca Rhuanny Tolentino Orientador: Pêssoa, Hilzeth de Luna Freire Abstract: Oral mucositis (OM) is an important acute adverse effect in the oral cavity in patients undergoing chemotherapy and/or radiotherapy. The lesions can lead to a considerable decrease in quality of life, causing difficulty in eating, pain or burning when swallowing and can represent a gateway for opportunistic infections. The scientific literature describes some palliative treatments for oral mucositis, however they do not bring great benefits for the prevention and/or treatment of the disease. Medicinal plants have strongly contributed to the development of new therapeutic strategies through their secondary metabolites, among them is Anacardium occidentale L., which has already shown that the bark, leaves and bark oil are used in medicinal preparations such as anti -inflammatory, and the gum has recently been used in both the pharmaceutical and food industries and has many pharmacological properties already described, such as healing, antibacterial, antifungal, gastroprotective, antidiarrheal and antitumor activity. To characterize and investigate the antibacterial, antioxidant and cytotoxic activities of Anacardium occidentale L. (cashew tree gum) exudate as na alternative possible for oral mucositis. The physical-chemical characterization was carried out regarding color, odor, solid appearance, pH and viscosity. The total, reducing and non-reducing sugars present in cashew tree gum were also analyzed. Antibacterial screening was carried out on Gram-positive and Gram-negative strains of clinical importance and collection, determining the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (CBM) against the selected strains. The combined use of cashew tree gum with synthetic antibacterials was evaluated using the infusion disc method. Subsequently, the activity of the gum on the formation and pre-formation of biofilms was evaluated. The oxidant and antioxidant activity on human hemoglobin was determined. Human blood samples of types A, B and O were subjected to cytotoxicity assessment at extract concentrations of 125μg/mL to 1000μg/mL against hemolytic and anti-hemolytic activity assays. Cashew tree gum presented an MIC and MBC of 1000µg/mL for Streptococcus mutans from the ATCC25175 collection and Pseudomonas aeruginosa from the ATCC9027 collection, with a bactericidal nature. It was possible to identify a synergistic effect when associated with azithromycin against the Pseudomonas aeruginosa strain and an indifferent effect against Streptococcus mutans. In relation to the biofilm, the cashew tree gum reduced the formation, but was not able to destroy the pre-formed biofilm. No oxidizing activity of the cashew tree gum was observed, but with regard to its antioxidant activity, it was found that the gum was able to reduce the effect of the oxidizing agent phenylhydrazine by 59.7%. In terms of hemolytic activity, at the concentrations tested, it presented low activity on human erythrocytes of the ABO system, and presented anti-hemolytic activity, reducing the degree of hemolysis caused by the hypotonic solution in type A blood by 42.78%, 62% in type B blood. and 49.96% in blood O. The data found demonstrate that cashew tree gum is a candidate for possible therapeutic applications against oral mucositis and its toxicity profile indicates feasibility for future studies. Editor: Universidade Federal da Paraíba Tipo: Tese 2024-06-28T00:00:00Z https://repositorio.ufpb.br/jspui/handle/123456789/37494 Título: Estudo pré-clínico do galato de etila sobre a reatividade vascular, coagulação secundária e atividade agregante de plaquetas em ratos Autor(es): Ramalho, Ricardo Cartaxo Orientador: Diniz, Margareth de Fátima Formiga Melo Abstract: Cardiovascular diseases (CVD) are established by the World Health Organization (WHO) as a group of conditions that affect blood vessels and the heart. CVDs represent the main cause of death globally, and Brazil is no exception. Data from DATASUS from 2022 indicate that approximately 27% of total deaths, that is, more than 400 thousand people, were caused by problems in the circulatory system in the year in question. Currently, the health system has several drugs used in CVD, but the quantity available for hemostatic diseases is still small. Therefore, it was decided to carry out a preclinical pharmacological analysis with derivatives of gallic acid, an important precursor of bioactive molecules, and verify their actions at the vascular level and hemostatic system, based on the possible vasorelaxant and antioxidant effect of ethyl gallate in isolated rings of superior mesenteric artery of rats, as well as to evaluate its anticoagulant and antiplatelet action. Ethyl gallate demonstrated an endothelium-dependent vasorelaxant and antioxidant effect that was inhibited by the presence of NG-nitro-L-arginina-metil ester (L-NAME) - (100 μmol L-1) or 1H[1,2,3]-oxadiazolo-[4,3-a]-quinoxalin-1ona (ODQ) - (10 μmol L-1). Arterial rings stimulated with angiotensin II (0.1 μmol L-1) had the formation of superoxide anions, analyzed by fluorescence microscopy, reduced by the presence of the gallic derivative. These results demonstrate the ability of ethyl gallate to cause vasorelaxation by activating the eNOS/NO/CGs pathway and to antagonize the pro-oxidant effect of angiotensin II in isolated rat mesenteric artery. In the evaluation of the anticoagulant and antiplatelet activity of ethyl gallate, the rats were distributed into five different groups: control group, ethyl gallate 5 mg.kg-1 group, ethyl gallate 50 mg.kg-1 group, enoxaparin 5 mg.kg-1 group, and ethyl gallate 5 mg.kg-1 + enoxaparin 5 mg.kg-1 group. The data demonstrate that ethyl gallate has an antiplatelet effect by inhibiting aggregation upon stimulation with ADP and, although it does not demonstrate a direct effect on plasma coagulation, it can potentiate the action of enoxaparin. Corroborating these results, ethyl gallate significantly reduces the occlusion time in the carotid artery treated with ferric chloride, as well as presenting a synergistic effect in animals treated concomitantly with enoxaparin. In conclusion, it can be highlighted that ethyl gallate showed relevant vasorelaxant and antioxidant potential and showed antithrombotic action and its possible usefulness in combination with other anticoagulants for the treatment of thrombotic disorders. It was also possible to demonstrate its promising antiplatelet activity with possible therapeutic application. Editor: Universidade Federal da Paraíba Tipo: Tese 2025-04-25T00:00:00Z