为了寻找关于细胞松弛素 B (2) 对肌动蛋白聚合的抑制作用的更全面的构效关系 (SAR)，进行了 2 与单体肌动蛋白的虚拟对接。这导致了2的潜在重要官能团（即异吲哚酮核心（N-2）的NH基团和C-7和C-20处的羟基）的鉴定，这些官能团参与与2的残余氨基酸的相互作用。肌动蛋白的结合袋。 2 在 C-7、N-2 和 C-20 位点的化学修饰产生了衍生物 3-6，并对其生物活性进行了分析。与 2 相比，化合物 3-5 在鼠 L929 成纤维细胞中表现出降低的细胞毒性或没有细胞毒性。此外，用 3-6 对人骨肉瘤细胞 (U-2OS) 进行短期和长期治疗会在不同程度上影响肌动蛋白网络，部分伴随着多核的诱导。在 C-20 和 N-2 处显示乙酰化的衍生物在细胞内缓慢转化为高细胞毒性 2。 总之，这项研究强调了 C-7 处的羟基和 N-2 处的 NH 功能对于 2 效力的重要性对肌动蛋白聚合的抑制作用。

In search of a more comprehensive structure-activity relationship (SAR) regarding the inhibitory effect of cytochalasin B (2) on actin polymerization, a virtual docking of 2 onto monomeric actin was conducted. This led to the identification of potentially important functional groups of 2 (i.e., the NH group of the isoindolone core (N-2) and the hydroxy groups at C-7 and C-20) involved in interactions with the residual amino acids of the binding pocket of actin. Chemical modifications of 2 at positions C-7, N-2, and C-20 led to derivatives 3-6, which were analyzed for their bioactivities. Compounds 3-5 exhibited reduced or no cytotoxicity in murine L929 fibroblasts compared to that of 2. Moreover, short- and long-term treatments of human osteosarcoma cells (U-2OS) with 3-6 affected the actin network to a variable extent, partially accompanied by the induction of multinucleation. Derivatives displaying acetylation at C-20 and N-2 were subjected to slow intracellular conversion to highly cytotoxic 2. Together, this study highlights the importance of the hydroxy group at C-7 and the NH function at N-2 for the potency of 2 on the inhibition of actin polymerization.