Synthesis and biological evaluation of novel tanshinone IIA derivatives for treating pain / 中国天然药物
Chinese Journal of Natural Medicines (English Ed.)
;
(6): 113-124, 2018.
Artigo
em Inglês
| WPRIM
| ID: wpr-773635
ABSTRACT
Due to ineffectiveness and side effects of existing analgesics, chronic pain has become one of the most complex and difficult problems in the clinic. Monoacylglycerol lipase (MAGL) is an essential hydrolase in the endocannabinoid system and has been identified as a potential target for the treatment of pain. In the present study, we designed and synthesized twelve tanshinone IIA analogs and screened their activity against MAGL. Selected compounds were tested for analgesic activity in vivo, with the acetic acid writhing test model. Among the test compounds, compound III-3 (IC 120 nmol·L) showed significant activity against MAGL and ameliorated the clinical progression in the mouse pain model. Additionally, compound III-3, substitution with N-methyl-2-morpholinoacetamide, demonstrated improved solubility relative to tanshinone IIA.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Relação Estrutura-Atividade
/
Química
/
Abietanos
/
Avaliação Pré-Clínica de Medicamentos
/
Tratamento Farmacológico
/
Inibidores Enzimáticos
/
Dor Crônica
/
Analgésicos
/
Metabolismo
/
Camundongos Endogâmicos ICR
Limite:
Animais
/
Feminino
/
Humanos
/
Masculino
Idioma:
Inglês
Revista:
Chinese Journal of Natural Medicines (English Ed.)
Ano de publicação:
2018
Tipo de documento:
Artigo
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