Gelatinase A, a zinc-containing endopeptidase, has been shown to be an essential therapeutic target for tumor intervention owing to its participation in almost all types of solid tumors. Based on our previous work with respect to quinoxalinone peptidomimetics, a novel series of sulphonamide-containing 1,4-dithia-7-azaspiro[4,4]nonane (DAN) derivatives have been synthesized and evaluated as potential gelatinase A inhibitors hereby. The results revealed that the majority of tested compounds displayed satisfactory inhibition activity against gelatinase A. Among the tested compounds, 2b, 3a, 4a–d, 6a, 6d, 7a–d exhibited more potent gelatinase A inhibition than the positive control LY52. Furthermore, two test compounds 2b and 6a demonstrated moderate anti-proliferative in vitro and anti-metastatic activities in vivo, which might be utilized as potential leads in future chemical optimization.

明胶酶A，一种含锌的内肽酶，由于其参与几乎所有类型的实体瘤而已被证明是肿瘤干预的重要治疗靶标。基于我们先前对喹喔啉酮拟肽的研究，已合成了一系列新的含磺酰胺的1,4-二硫杂-7-azaspiro [4,4]壬烷（DAN）衍生物，并据此评估其为潜在的明胶酶A抑制剂。结果表明，大多数被测化合物对明胶酶A表现出令人满意的抑制活性。在被测化合物中，2b，3a，4a - d，6a，6d，7a - d与阳性对照LY52相比，它具有更强的明胶酶A抑制作用。此外，两种测试化合物2b和6a表现出适度的体外抗增殖活性和体内抗转移活性，可用作未来化学优化中的潜在先导。