Data/hora: 28/05/2024 17:02:15

Provedor de dados: | Genetics and Molecular Biology
País: | Brazil
Título: | In vivo chemotherapeutic insight of a novel isocoumarin (3-hexyl-5,7-dimethoxy-isochromen-1-one): Genotoxicity, cell death induction, leukometry and phagocytic evaluation
Autores: | Araújo,Flávio Henrique Souza de; Figueiredo,Débora Rojas de; Auharek,Sarah Alves; Pesarini,João Renato; Meza,Alisson; Gomes,Roberto da Silva; Monreal,Antônio Carlos Duenhas; Antoniolli-Silva,Andréia Conceição Milan Brochado; Lima,Dênis Pires de; Kassuya,Candida Aparecida Leite; Beatriz,Adilson; Oliveira,Rodrigo Juliano.
Data: | 2017-09-01
Ano: | 2017
Palavras-chave: | Isocoumarin synthesis; Genotoxicity; Splenic phagocytosis; Chemotherapy.
Resumo: | Abstract Chemotherapy is one of the major approaches for the treatment of cancer. Therefore, the development of new chemotherapy drugs is an important aspect of medicinal chemistry. Chemotherapeutic agents include isocoumarins, which are privileged structures with potential antitumoral activity. Herein, a new 3-substituted isocoumarin was synthesized from 2-iodo-3,5-dimethoxy-benzoic acid and oct-1-yne in a cross-coupling Sonogashira reaction followed by a copper iodide-catalyzed intramolecular cyclization as key step using MeOH/Et3N as the solvent system. The present study also evaluated the leukometry, phagocytic activity, genotoxic potential and cell death induction of three different doses (5 mg/kg, 10 mg/kg and 20 mg/kg) of this newly synthesized isocoumarin, alone and in combination with the commercial chemotherapeutic agents cyclophosphamide (100 mg/kg) and cisplatin (6 mg/kg) in male Swiss mice. The results suggest that the isocoumarin has genotoxicity and causes cell death. Noteworthy, this new compound can increase splenic phagocytosis and lymphocyte frequency, which are related to immunomodulatory activity. When combined with either cyclophosphamide or cisplatin, chemopreventive activity led to a reduction in the effects of both chemotherapeutic drugs. Thus, the new isocoumarin is not a candidate for chemotherapeutic adjuvant in treatments using cyclophosphamide or cisplatin. Nevertheless, the compound itself is an important prototype for the development of new antitumor drugs.
Tipo: | Info:eu-repo/semantics/article
Idioma: | Inglês
Identificador: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572017000400665
Editor: | Sociedade Brasileira de Genética
Relação: | 10.1590/1678-4685-gmb-2016-0316
Formato: | text/html
Fonte: | Genetics and Molecular Biology  v.40 n.3 2017
Fonte: | info:eu-repo/semantics/openAccess