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[计算机模拟筛选微管蛋白聚合抑制剂]

[In silico Search for Tubulin Polymerization Inhibitors].

作者信息

Sahakyan H K, Arakelov G G, Nazaryan K B

机构信息

Russian-Armenian University, Yerevan, 0051 Armenia.

Institute of Molecular Biology, National Academy of Sciences of the Republic of Armenia, Yerevan, 0014 Armenia.

出版信息

Mol Biol (Mosk). 2018 Jul-Aug;52(4):699-704. doi: 10.1134/S0026898418040171.

Abstract

Cytostatic colchicine is widely used in the treatment of Familial Mediterranean fever, but it has several side effects. For finding new, more effective drugs with higher affinity and diminishside effects we carried out virtual screening of potential inhibitors of the main target of colchicine, the polymerization of tubulin by evaluating affinity 25745 compounds, structurally related to the colchicine. We have identified 11 commercially available compounds with higher affinity to tubulin. Compounds with highest binding scores include trimethoxybenzene and its derivatives; these compounds bind to the same site in similar orientation. Information provided can form the basis for design of new cytostatics.

摘要

细胞抑制药物秋水仙碱广泛用于治疗家族性地中海热,但它有多种副作用。为了找到新的、更有效的药物,这些药物具有更高的亲和力并减少副作用,我们通过评估与秋水仙碱结构相关的25745种化合物对微管蛋白聚合这一秋水仙碱主要靶点的亲和力,进行了潜在抑制剂的虚拟筛选。我们已经鉴定出11种对微管蛋白具有更高亲和力的市售化合物。结合分数最高的化合物包括三甲氧基苯及其衍生物;这些化合物以相似的方向结合到相同的位点。所提供的信息可为新型细胞抑制剂的设计奠定基础。

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