通过对已批准的药物化合物的计算机查来搜索乙胆酶抑制剂
T A Materova1, A V Sulimov2, I S Ilin2
1Department of Physics, Lomonosov Moscow State University, Moscow, Russia.
计算查发现了新的药物候选物来抑制乙胆酶 (AChE),一种对认知功能至关重要的酶. 这些发现为阿尔茨海默氏症等神经退行性疾病提供了潜在的新疗法.
科学领域:
- 生物化学 生物化学
- 计算化学的计算化学
- 神经科学是一个神经科学.
背景情况:
- 乙胆酶 (AChE) 对于神经传递和认知功能至关重要.
- AChE的失调与神经退行性疾病有关,尤其是阿尔茨海默病.
- 识别新型ACHE抑制剂对于开发有效治疗方法至关重要.
研究的目的:
- 通过计算选已批准的药物化合物以检测潜在的乙胆酶 (AChE) 抑制.
- 确定具有神经退行性疾病治疗潜力的新型化学实体.
主要方法:
- 使用分子对接 (SOL程序,MMFF94力场,遗传算法) 对2909个已批准的药物化合物的虚拟选.
- 针对人类的ACHE结构 (PDB ID: 6O4W).
- 使用量子化学计算 (PM7方法,COSMO溶剂模型) 进行后处理,以确定结合度.
主要成果:
- 最初的对接确定了211个有前途的连接体.
- 量子化学计算完善了选择,确定了16名顶级候选人.
- 值得注意的化合物包括Pixantrone,Guanfacine和Hydroxystilbamidine,来自不同的化学类.
结论:
- 该研究成功地从现有的药物库中识别出新的,潜在的乙胆酶抑制剂 (AChE).
- 这些化合物,包括Pixantrone,Guanfacine和Hydroxystilbamidine,代表了阿尔茨海默病和其他神经退行性疾病的有希望的线索.
- 鉴定的抑制剂的多样化化学结构突出显示了广泛的治疗潜力.
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