【摘要】 目的吴茱萸碱和吴茱萸次碱是中药吴茱萸中的主要生物碱成分,二者可以通过激活辣椒素受体(TRPV1)释放CGRP达到舒张血管降低血压的作用。本课题研究了吴茱萸次碱的母核构像与辣椒素受体有关的药理作用的选择性关系。方法本研究设计、合成了两个5-脱氧吴茱萸次碱的类似物,并分别测试它们对动脉环和气管环的影响。结果这两个化合物均能产生弱于吴茱萸次碱的舒张血管作用,且它们与吴茱萸次碱一样不能产生任何支气管收缩作用。结论计算机模拟显示这两个化合物有着与吴茱萸次碱类似的近平面结构,而这种近平面的结构可能是它们不能产生支气管收缩作用的原因。实验结果为研究TRPV1亚型,开发新一代以TRPV1为靶点的低副作用的抗高血压药物指出了新的方向。更多还原

【Abstract】 【Objective】To investigate the relationship between the scaffold conformation in the structure of rutaecarpine and the selectivity of pharmacological effects associated with TRPV1 receptor.【Methods】Two 5-deoxyrutaecarpine analogs were designed and synthesized. Their effects on the aortic rings and bronchial rings were tested in vitro. 【Results】The results showed that the 5-deoxy-rutaecarpine analogs had lower vasodilator activities than rutaecarpine and both of them couldn’t cause bronchoconstriction at tested concentrations.【Conclusions】The simulation of these two compounds has showed their essential planar structures are similar to that of rutaecarpine. The difference between evodiamine and rutaecarpine in the bronchoconstriction might be related to their three-dimensional structures. The results have suggested a new direction of valuable TRPV1 agonist as anti-hypertensive drugs.更多还原