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 endo...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_(50) 120 nmol·L^(-1)) 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.展开更多
基金supported by the Key Research&Development Program in Jiangsu(No.BE2015683)the Introduction Program of Leading Scientific and Technological Entrepreneurship in Nanjing(No.2013B14007)
文摘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_(50) 120 nmol·L^(-1)) 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.
