Anti-Hyperuricemic, Anti-Arthritic, Hemolytic Activity and Therapeutic Safety of Glycoconjugated Triazole-Phthalimides
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,
Vera Lúcia de Menezes Lima
Affiliations
José Guedes da Silva
Laboratório de Lipídeos e Aplicações de Biomoléculas em Doenças Prevalentes e Negligenciadas (LAB—DPN), Centro de Biociências, Departamento de Bioquímica, Universidade Federal de Pernambuco, Recife 50670-901, PE, Brazil
André de Lima Aires
Centro de Ciências Médicas—Área Acadêmica de Medicina Tropical, Universidade Federal de Pernambuco, Recife 50670-901, PE, Brazil
Rebeca Xavier da Cunha
Laboratório de Lipídeos e Aplicações de Biomoléculas em Doenças Prevalentes e Negligenciadas (LAB—DPN), Centro de Biociências, Departamento de Bioquímica, Universidade Federal de Pernambuco, Recife 50670-901, PE, Brazil
Talyta Valéria Siqueira do Monte
Centro de Ciências da Saúde (CCS), Departamento de Enfermagem, Universidade Federal de Pernambuco, Recife 50670-901, PE, Brazil
Shalom Pôrto de Oliveira Assis
Laboratório de Biotecnologia e Ciências Ambientais (NPCIAMB), Departamento de Medicina, Universidade Católica de Pernambuco (UNICAP), Recife 50050-900, PE, Brazil
Ronaldo Nascimento de Oliveira
Laboratório de Síntese de Compostos Bioativos (LSCB), Departamento de Química, Universidade Federal Rural de Pernambuco (UFRPE), Recife 52171-900, PE, Brazil
Talita Giselly dos Santos Souza
Laboratório de Biotecnologia e Fármacos, Centro Acadêmico de Vitória (CAV), Universidade Federal de Pernambuco (UFPE), Recife 50670-901, PE, Brazil
Cristiano Aparecido Chagas
Laboratório de Biotecnologia e Fármacos, Centro Acadêmico de Vitória (CAV), Universidade Federal de Pernambuco (UFPE), Recife 50670-901, PE, Brazil
Jacinto da Costa Silva Neto
Laboratório de Pesquisas Citológicas e Moleculares (LPCM), Universidade Federal de Pernambuco (UFPE), Recife 50670-901, PE, Brazil
Hallysson Douglas Andrade de Araújo
Laboratório de Lipídeos e Aplicações de Biomoléculas em Doenças Prevalentes e Negligenciadas (LAB—DPN), Centro de Biociências, Departamento de Bioquímica, Universidade Federal de Pernambuco, Recife 50670-901, PE, Brazil
Vera Lúcia de Menezes Lima
Laboratório de Lipídeos e Aplicações de Biomoléculas em Doenças Prevalentes e Negligenciadas (LAB—DPN), Centro de Biociências, Departamento de Bioquímica, Universidade Federal de Pernambuco, Recife 50670-901, PE, Brazil
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 (<3%). Our data demonstrate that the new glycoconjugate triazole-phthalimides have potential to treat hyperuricemia and its secondary complications, such as gouty arthritis, with a low to non-significant rate of erythrocytes hemolysis, genotoxicity and mutagenicity making these molecules strong candidates as pharmaceutical agents for treatment requiring uric-acid-lowering therapy.
