State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guiyang, People's Republic of China.
College of Pharmacy, Guizhou University, Guiyang, People's Republic of China.
J Enzyme Inhib Med Chem. 2021 Dec;36(1):1996-2009. doi: 10.1080/14756366.2021.1975695.
Microtubule dynamics are crucial for multiple cell functions, and cancer cells are particularly sensitive to microtubule-modulating agents. Here, we describe the design and synthesis of a series of ()-2-(5-benzylidene-4-oxo-2-thioxothiazolidin-3-yl)--phenylacetamide derivatives and evaluation of their microtubule-modulating and anticancer activities . Proliferation assays identified as the most potent of the antiproliferative compounds, with 50% inhibitory concentrations ranging from 7.0 to 20.3 µM with A549, PC-3, and HepG2 human cancer cell lines. Compound also disrupted cancer A549 cell migration in a concentration-dependent manner. Immunofluorescence microscopy, transmission electron microscopy, and tubulin polymerisation assays suggested that compound promoted protofilament assembly. In support of this possibility, computational docking studies revealed a strong interaction between compound and tubulin Arg 369, which is also the binding site for the anticancer drug Taxol. Our results suggest that ()-2-(5-benzylidene-4-oxo-2-thioxothiazolidin-3-yl)--phenylacetamide derivatives could have utility for the development of microtubule-stabilising therapeutic agents.
微管动力学对于多种细胞功能至关重要，而癌细胞对微管调节药物特别敏感。在这里，我们描述了一系列（）-2-（5-亚苄基-4-氧代-2-噻唑烷-3-基）-苯乙酰胺衍生物的设计和合成，并评估了它们的微管调节和抗癌活性。增殖实验确定 是最有效的抗增殖化合物之一，对 A549、PC-3 和 HepG2 人癌细胞系的 50%抑制浓度范围为 7.0 至 20.3μM。化合物 还以浓度依赖的方式破坏了癌细胞 A549 的迁移。免疫荧光显微镜、透射电子显微镜和微管聚合实验表明，化合物 促进原纤维组装。支持这种可能性的计算对接研究表明，化合物 与微管 Arg369 之间存在强烈相互作用，Arg369 也是抗癌药物紫杉醇的结合位点。我们的结果表明，（）-2-（5-亚苄基-4-氧代-2-噻唑烷-3-基）-苯乙酰胺衍生物可能对开发微管稳定的治疗药物具有实用价值。
