Rho家族GTP酶调节细胞过程并促进肿瘤生长和转移；因此，RhoA是抑制肿瘤转移的潜在靶点。然而，RhoA靶向抗癌药物的开发进展有限。在这里，我们基于我们之前研究中报道的 RhoA 共价抑制剂 (DC-Rhoin) 合成了苯并[b]噻吩-3-羧酸 1,1-二氧化物衍生物。观察到的结构-活性关系（由C-3中的甲酰胺和C-5中的1-甲基-1H-吡唑贡献）增强了衍生物的抗增殖活性。化合物b19显着抑制MDA-MB-231细胞的增殖、迁移和侵袭，并促进其凋亡。肌球蛋白轻链磷酸化的抑制和应激纤维的形成证实了 b19 通过 RhoA/ROCK 途径的抑制活性。正如分子对接分析中所观察到的，b19 表现出与 DC-Rhoin 不同的结合模式。该研究为靶向RhoA/ROCK通路的抗癌药物的开发提供参考。

Rho family GTPases regulate cellular processes and promote tumour growth and metastasis; thus, RhoA is a potential target for tumour metastasis inhibition. However, limited progress has been made in the development of RhoA targeting anticancer drugs. Here, we synthesised benzo[b]thiophene-3-carboxylic acid 1,1-dioxide derivatives based on a covalent inhibitor of RhoA (DC-Rhoin), reported in our previous studies. The observed structure-activity relationship (contributed by carboxamide in C-3 and 1-methyl-1H-pyrazol in C-5) enhanced the anti-proliferative activity of the derivatives. Compound b19 significantly inhibited the proliferation, migration, and invasion of MDA-MB-231 cells and promoted their apoptosis. The suppression of myosin light chain phosphorylation and the formation of stress fibres confirmed the inhibitory activity of b19 via the RhoA/ROCK pathway. b19 exhibited a different binding pattern from DC-Rhoin, as observed in molecular docking analysis. This study provides a reference for the development of anticancer agents targeting the RhoA/ROCK pathway.