标题：Sulphonamide 1,4-dithia-7-azaspiro[4,4]nonane derivatives as gelatinase A inhibitors
作者机构：[Shi, L] Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Ji'nan, Shandong 250012, 更多
通讯作者地址：[Li, X]Shandong Univ, Key Lab Chem Biol, Minist Educ, Sch Pharmaceut Sci, Jinan 250012, Shandong, Peoples R China.
来源：Bioorganic and medicinal chemistry
关键词：1;4-Dithia-7-azaspiro[4;4]nonane (DAN);Anti-proliferative;Docking study;Gelatinase A inhibitors;Sulphonamide
摘要：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.