title: Sulphonamide 1,4-dithia-7-azaspiro[4,4]nonane derivatives as gelatinase A inhibitors.
abstract: 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.
authors.affiliation: Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Ji'nan, Shandong 250012, China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Shi
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Haina
authors.initials: H
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Li
authors.forename: Xun
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018093:Gelatinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D061965:Matrix Metalloproteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009362:Neoplasm Metastasis / Q000188:drug therapy; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; D013141:Spiro Compounds; D013449:Sulfonamides; D018093:Gelatinases
keywords: 1,4-Dithia-7-azaspiro[4,4]nonane (DAN); Anti-proliferative; Docking study; Gelatinase A inhibitors; Sulphonamide