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2 results on '"Shalom Pôrto de Oliveira Assis"'

1. Anti-Hyperuricemic, Anti-Arthritic, Hemolytic Activity and Therapeutic Safety of Glycoconjugated Triazole-Phthalimides

Author

José Guedes da Silva, André de Lima Aires, Rebeca Xavier da Cunha, Talyta Valéria Siqueira do Monte, Shalom Pôrto de Oliveira Assis, Ronaldo Nascimento de Oliveira, Talita Giselly dos Santos Souza, Cristiano Aparecido Chagas, Jacinto da Costa Silva Neto, Hallysson Douglas Andrade de Araújo, and Vera Lúcia de Menezes Lima

Subjects
hyperuricemia, arthritis, medicinal chemistry, uric acid, gouty arthritis, Biology (General), QH301-705.5
Abstract

Hyperuricemia, the metabolic alteration that leads to gout or gouty arthritis, is increasing worldwide. Glycoconjugated triazole-phthalimides show potent anti-inflammatory activity. The aim of this study was to evaluate the anti-hyperuricemia effect of glycoconjugated triazole-phthalimides. To develop hyperuricemia, groups of mice received orally potassium oxonate (250 mg/kg) for 7 days, and F2, F3 and F4 glycoconjugated triazole-phthalimides (20 mg/kg), allopurinol (300 mg/kg), and 1% carboxymethylcellulose; indomethacin (2 and 4 mg/kg) was the positive control for anti-arthritic effect. Genotoxic and mutagenic effects were evaluated by the comet and micronucleus assays, respectively. The hemolytic action of the compounds was evaluated. Phthalimides F2, F3 and F4 significantly reduced the levels of serum uric acid, creatinine and urea in hyperuricemic animals. In addition, the compounds were efficient in reducing protein denaturation in a dose-dependent manner. In an interesting way, the histopathological analysis of kidneys from groups treated with F2, F3 and F4 showed a glomerular architecture, with the Bowman’s capsule and renal tubules having a normal appearance and without inflammatory changes. Also, F2 and F4 showed a small increase in micronuclei, indicating a low mutagenic effect, whilst by comet assay only, we could infer that F4 affected the frequency and damage index, thus indicating a very small genotoxic action. Similarly, the phthalimides showed a low degree of erythrocyte hemolysis (

Published
2023
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2. Antihyperlipidemic Activity of Glycoconjugated Phthalimides in Mice Submitted to a Model of Dyslipidemia and Insulin Resistance

Author

José Guedes da Silva Júnior, Hallysson Douglas Andrade de Araújo, Ismael Gomes da Rocha, Jacinto Costa da Silva Neto, Ronaldo Nascimento Oliveira, Shalom Pôrto de Oliveira Assis, and Vera Lúcia de Menezes Lima

Subjects
Simvastatin, Insulins, Phthalimides, Bioengineering, Cholesterol, LDL, General Chemistry, General Medicine, Lipoproteins, VLDL, Biochemistry, Hormones, Uric Acid, Mice, Diabetes Mellitus, Type 2, Carboxymethylcellulose Sodium, Animals, Molecular Medicine, Obesity, Insulin Resistance, Molecular Biology, Triglycerides, Transaminases, Hypolipidemic Agents, Dyslipidemias
Abstract

Alterations in lipid and lipoprotein metabolism are factors that trigger several negative metabolic complications. Hyperlipidemia is the starting point for the development of comorbidities of the cardiovascular system, such as atherosclerosis. The search for compounds that reduce high levels of total cholesterol and triglycerides has been widely reported in several publications in the literature. Phthalimide derivatives have been extensively researched with various biological actions. In this study we evaluated the antihyperlipidemic ability of three phthalimide derivatives (FGT-2, FGT-3 and FGT-4) on a model of obesity and insulin resistance in mice. The animals were submitted to a hyperlipid diet for 60 days. On the thirtieth day they were treated with phthalimides (20 mg/kg). The positive control group was treated with Simvastatin (20 mg/kg) and the negative control received only the carboxymethylcellulose vehicle. Biochemical and histological analyzes of all groups were analyzed. The animals treated with phthalimidic derivatives had a reduction in total cholesterol, low density and very low density lipoproteins (LDL-c and VLDL-c), triglycerides and fasting glycemia when compared to the negative control group. The treated animals also showed good results when analyzing the atherogenic indexes Castelli i and II and the ratio Triglycerides/HDL-c. In the oral glucose tolerance test and in the insulin tolerance test, animals treated with phthalimides were more sensitive to the action of the hormone regulating carbohydrate uptake. In the evaluation of the transaminases (AST/ALT), the animals of the group treated with phthalimides presented a lower elevation than the other groups of the experiment, the same observed with the uric acid evaluation. Histological analyzes were performed on liver, kidney, heart and pancreas samples. The groups treated with the compounds FGT-2 and FGT3 presented discrete alterations in the liver and kidney. FGT-4 did not present histological alterations for both tissues and the three phthalimide derivatives did not cause alterations in the other organs. These results suggest that the phthalimides tested can act as antihyperlipidemic agents and have a pleiotropic action, by acting also reducing glycemia in insulin resistance model mimicking diabetes mellitus type 2. These compounds may appear as a new approach in the treatment of obesity and complications, which are multifaceted.

Published
2022

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