School of Pharmaceutical Science, Zhengzhou University, Zhengzhou 450001, China.
Henan Provincial Key Laboratory Of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, China.
Curr Top Med Chem. 2020;20(17):1505-1508. doi: 10.2174/1568026620999200616132924.
Butterfly-shaped structure, as a novel scaffold with an attractive and certain shape, has been widely used in new drug discovery. Tubulin, composing of α- and β-tubulin heterodimers, plays a key role in mitosis and cell division which are regarded as an excellent target for cancer therapy. Currently, a series of butterfly shape diaryl heterocyclic compounds have been reported with strong potential against the tubulin-colchicine binding site. It is with one ring buried in the β subunit, another ring interacts with the α subunit and the main body is located in the flat pocket. Here, we firstly introduce the concept of butterfly structure for the tubulin inhibitors, focusing on the latest advancements in a variety of molecules bearing butterfly structure, and then highlight the challenges and future direction of butterfly structure- based tubulin-colchicine binding site inhibitors.
蝶形结构作为一种具有吸引力和确定性形状的新型支架,已被广泛应用于新药发现。微管蛋白由α-和β-微管蛋白异二聚体组成,在有丝分裂和细胞分裂中起着关键作用,被认为是癌症治疗的一个极好的靶点。目前,已经报道了一系列具有强烈抑制微管蛋白-秋水仙素结合部位的蝶形二芳基杂环化合物。该化合物的一个环埋在β亚基中,另一个环与α亚基相互作用,主体位于平口袋中。在这里,我们首先为微管蛋白抑制剂引入蝶形结构的概念,重点介绍各种带有蝶形结构的分子的最新进展,然后强调基于蝶形结构的微管蛋白-秋水仙素结合部位抑制剂所面临的挑战和未来方向。