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Acute toxicity and antitumor potential of 1,3,4-trisubstituted-1,2,3-triazole dhmtAc-loaded liposomes on a triple-negative breast cancer model.
Ramos, Jonas P; Abdel-Salam, Mostafa A L; Nobre, Daniel A B; Glanzmann, Nicolas; de Souza, Camila P; Leite, Elaine A; de Abreu Teles, Pedro P; Barbosa, Alan S; Barcelos, Luciola S; Dos Reis, Diego C; Cassali, Geovanni D; de Lima, Maria E; de Castro, Quênia J T; Grabe-Guimarães, Andrea; da Silva, Adilson D; de Souza-Fagundes, Elaine M.
Afiliación
  • Ramos JP; Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
  • Abdel-Salam MAL; Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
  • Nobre DAB; Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
  • Glanzmann N; Departamento de Química, Universidade Federal de Juiz de Fora, Juiz de Fora, Brazil.
  • de Souza CP; Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
  • Leite EA; Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
  • de Abreu Teles PP; Departamento de Patologia Geral, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
  • Barbosa AS; Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
  • Barcelos LS; Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
  • Dos Reis DC; Departamento de Patologia Geral, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
  • Cassali GD; Departamento de Patologia Geral, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
  • de Lima ME; Programa de Pós-Graduação em Medicina-Biomedicina, Faculdade Santa Casa de Belo Horizonte, Belo Horizonte, Brazil.
  • de Castro QJT; Departamento de Farmácia, Escola de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto, Brazil.
  • Grabe-Guimarães A; Departamento de Farmácia, Escola de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto, Brazil.
  • da Silva AD; Departamento de Química, Universidade Federal de Juiz de Fora, Juiz de Fora, Brazil.
  • de Souza-Fagundes EM; Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Arch Pharm (Weinheim) ; 355(9): e2200004, 2022 Sep.
Article en En | MEDLINE | ID: mdl-35621705
For the first time, compounds developed from the 1,2,3-triazole scaffold were evaluated as novel drugs to treat triple-negative breast cancer (TNBC). Four organic salts were idealized as nonclassical bioisosteres of miltefosine, which is used in the topical treatment for skin metastasizing breast carcinoma. Among them, derivative dhmtAc displayed better solubility and higher cytotoxicity against the human breast adenocarcinoma cell line and mouse 4T1 cell lines, which are representatives of TNBC. In vitro assays revealed that dhmtAc interferes with cell integrity, confirmed by lactate dehydogenase leakage. Due to its human peripheral blood mononuclear cell (PBMC) toxicity, dhmtAc in vivo studies were carried out with the drug incorporated in a long-circulating and pH-sensitive liposome (SpHL-dhmtAc), and the acute toxicity in BALB/c mice was determined. Free dhmtAc displayed cardiac and pulmonary toxicity after the systemic administration of 5 mg/kg doses. On the other hand, SpHL-dhmtAc displayed no toxicity at 20 mg/kg. The in vivo antitumor effect of SpHL-dhmtAc was investigated using the 4T1 heterotopic murine model. Intravenous administration of SpHL-dhmtAc reduced the tumor volume and weight, without interfering with the body weight, compared with the control group and the dhmtAc free form. The incorporation of the triazole compound in the liposome allowed the demonstration of its anticancer potential. These findings evidenced 1,3,4-trisubstituted-1,2,3-triazole as a promising scaffold for the development of novel drugs with applicability for the treatment of patients with TNBC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama Triple Negativas / Liposomas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Arch Pharm (Weinheim) Año: 2022 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Alemania
Texto completo
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Imprimir
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama Triple Negativas / Liposomas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Arch Pharm (Weinheim) Año: 2022 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Alemania