通过 M 型毒蕈碱受体激活设计并合成两种具有心力衰竭生物活性的新型甾体衍生物。
Design and synthesis of two new steroid derivatives with biological activity on heart failure via the M-muscarinic receptor activation.
机构信息
Laboratory of Pharmaco-Chemistry at the Faculty of Chemical Biological Sciences of the University Autonomous of Campeche, Av. Agustín Melgar s/n, Col Buenavista, C.P. 24039 Campeche Cam., Mexico.
Laboratory of Pharmaco-Chemistry at the Faculty of Chemical Biological Sciences of the University Autonomous of Campeche, Av. Agustín Melgar s/n, Col Buenavista, C.P. 24039 Campeche Cam., Mexico.
出版信息
Steroids. 2020 Jun;158:108620. doi: 10.1016/j.steroids.2020.108620. Epub 2020 Feb 29.
Several drugs have been prepared to treat of heart failure using some protocols which require dangerous reagents and specific conditions. The aim of this study was to synthesize a series of steroid derivatives (compounds 2 to 18) using some chemical strategies. The biological activity of steroid derivatives against heart failure was evaluated using an ischemia/reperfusion model. In addition, the effect exerted by compounds 4 or 5 on left ventricular pressure was evaluated in the absence or presence of yohimbine, butaxamine and methoctramine. The results showed that 1) both compounds 4 or 5 significantly decrease the heart failure (translated as infarct area) compared with the compounds 2, 3 and 6-18. In addition, the compound 4 and 5 decreased the left ventricular pressure in a dose-dependent manner and this effect was significantly inhibited in the presence of methoctramine (p = 005). In conclusion, the compounds 4 or 5 decrease both the infarct area and left ventricular pressure via M-muscarinic receptor activation.
已经有几种药物被制备出来用于治疗心力衰竭，这些药物使用了一些需要危险试剂和特定条件的方案。本研究的目的是使用一些化学策略合成一系列甾体衍生物（化合物 2 至 18）。使用缺血/再灌注模型评估了甾体衍生物对心力衰竭的生物活性。此外，在不存在或存在育亨宾、丁氧胺和甲硫环胺的情况下，评估了化合物 4 或 5 对左心室压力的影响。结果表明：1）与化合物 2、3 和 6-18 相比，化合物 4 或 5 均能显著降低心力衰竭（梗死面积）。此外，化合物 4 和 5 以剂量依赖性方式降低左心室压力，而这种作用在存在甲硫环胺时被显著抑制（p=0.05）。总之，化合物 4 或 5 通过 M-毒蕈碱受体的激活来降低梗死面积和左心室压力。
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