Based on the co-crystal structures of tubulin with plinabulin and Compound 1 (a derivative of plinabulin), a total of 18 novel plinabulin derivatives were designed and synthesized. Their biological activities were evaluated against human pancreatic cancer BxPC-3 cell lines. Two novel Compounds 13d and 13e exhibited potent activities with IC₅₀ at 1.56 and 1.72 nM, respectively. The tubulin polymerization assay indicated that these derivatives could inhibit microtubule polymerization. Furthermore, the interaction between tubulin and these compounds were elucidated by molecular docking. The binding modes of Compounds 13d and 13e were similar to the co-crystal structure of Compound 1. H-π interaction was observed between the aromatic hydrogen of thiophene moiety with Phe20, which could enhance their binding affinities.

基于微管蛋白与纤毛蛋白和化合物1（纤毛蛋白的衍生物）的共晶体结构，总共设计和合成了18种新型纤毛蛋白衍生物。评估了它们对人胰腺癌BxPC-3细胞系的生物学活性。两种新颖的化合物13d和13e的有效活性分别为IC ₅₀为1.56和1.72 nM。微管蛋白聚合测定表明这些衍生物可以抑制微管聚合。此外，通过分子对接阐明了微管蛋白与这些化合物之间的相互作用。化合物13d和13e的结合模式与化合物的共晶体结构相似1。在噻吩部分的芳香氢与Phe20之间观察到H-π相互作用，这可以增强它们的结合亲和力。