布鲁顿酪氨酸激酶 (BTK) 是治疗多种人类 B 细胞相关自身免疫性疾病、炎症和血液恶性肿瘤的有前景的分子靶点。各种癌组织中的致病性改变依赖于突变体BTK的细胞增殖和存活，并且BTK也在一系列造血细胞中过度表达。因此，BTK正在成为治疗多种人类疾病的潜在药物靶点，多种可逆和不可逆抑制剂已经开发和正在开发中。因此，经过临床验证的 BTK 抑制作为一种抗癌治疗方法，在 B 细胞恶性肿瘤和实体瘤领域引起了极大的兴趣。本研究的重点是设计和合成新型羟吲哚磺酰胺衍生物，作为有前景的 BTK 抑制剂，且脱靶效应可忽略不计。具有较高碱性的最具细胞毒性的化合物是 PID-4 (2.29 ± 0.52 µM)、PID-6 (9.37 ± 2.47 µM) 和 PID-19 (2.64 ± 0.88 µM)。这些化合物对伯基特淋巴瘤 RAMOS 细胞产生选择性抑制，而对非 BTK 癌细胞系和非癌细胞系没有显着的细胞毒性。此外，PID-4 在抑制 BTK 和下游信号级联方面表现出良好的活性。作为 Burkitt 淋巴瘤细胞的有效抑制剂，PID-4 是开发新型化疗药物的有前景的先导药物。© 2023 Wiley-VCH GmbH。

Bruton's tyrosine kinase (BTK) is a promising molecular target for several human B-cell-related autoimmune disorders, inflammation, and haematological malignancies. The pathogenic alterations in various cancer tissues depend on mutant BTK for cell proliferation and survival, and BTK is also overexpressed in a range of hematopoietic cells. Due to this, BTK is emerging as a potential drug target to treat various human diseases, and several reversible and irreversible inhibitors have been developed and are being developed. As a result, BTK inhibition, clinically validated as an anticancer treatment, is finding great interest in B-cell malignancies and solid tumours. This study focuses on the design and synthesis of new oxindole sulfonamide derivatives as promising inhibitors of BTK with negligible off-target effects. The most cytotoxic compounds with greater basicity were PID-4 (2.29 ± 0.52 µM), PID-6 (9.37 ± 2.47 µM), and PID-19 (2.64 ± 0.88 µM). These compounds caused a selective inhibition of Burkitt's lymphoma RAMOS cells without significant cytotoxicity in non-BTK cancerous and non-cancerous cell lines. Further, PID-4 showed promising activity in inhibiting BTK and downstream signalling cascades. As a potent inhibitor of Burkitt's lymphoma cells, PID-4 is a promising lead for developing novel chemotherapeutics.© 2023 Wiley-VCH GmbH.