摘要
临床上可行的二甲双胍类似物的开发在很大程度上是一个需要克服的挑战。尽管它是一种非常有效的治疗 2 型糖尿病的药物,但进行了多项研究以寻求提高其降血糖活性或改善口服吸收率低和胃肠道副作用发生率等方面。此外,人们已经努力归因于新的活动,甚至扩展现有的活动,这些活动可以增强其对糖尿病的影响,例如胰腺保护、抗氧化和抗炎活动。在本文中,我们描述了过去三十年开发的二甲双胍类似物,强调缺乏基于计算的合理方法来指导它们的开发。我们还讨论了这可能是母体药物作用机制不明确的结果,并强调了最近在建立二甲双胍主要分子靶点方面取得的进展。我们还通过分子对接分析探讨了二甲双胍、丁双胍和苯乙双胍与线粒体呼吸链复合物 I 的结合,并回顾了应用计算工具提高此类类似物开发成功率的前景。因此,很明显,二甲双胍广泛的分子靶标和多种活性使该药物成为开发新实体的有前途的原型,特别是用于治疗 2 型糖尿病。
关键词: 双胍类,二甲双胍,糖尿病,分子靶标,复合物I,乳酸酸中毒。
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