title: Chromen-based TNF-alpha converting enzyme (TACE) inhibitors: design, synthesis, and biological evaluation.
abstract: A series of coumarin types MMP inhibitors were designed based on gelastatin hydroxamates (1) and evaluated for TACE, cellular TNF-alpha, and NO inhibitory activities. Among them, compounds 9b had potent inhibitory activities in enzymatic and cellular assays and good selectivity to MMP-2 and MMP-9. Further investigation of 9b will be carried out for its efficacy in RA animal model system.
authors.affiliation: Department of Biotechnology, Yonsei University, Seodaemun-gu, Seoul 120-740, Republic of Korea.
authors.forename: Kwangwoo
authors.initials: K
authors.lastname: Chun
authors.forename: Song-Kyu
authors.initials: SK
authors.lastname: Park
authors.forename: Hwan Mook
authors.initials: HM
authors.lastname: Kim
authors.forename: Yongseok
authors.initials: Y
authors.lastname: Choi
authors.forename: Myung-Hwa
authors.initials: MH
authors.lastname: Kim
authors.forename: Chun-Ho
authors.initials: CH
authors.lastname: Park
authors.forename: Bo-Young
authors.initials: BY
authors.lastname: Joe
authors.forename: Tae Gyu
authors.initials: TG
authors.lastname: Chun
authors.forename: Hyun-Moo
authors.initials: HM
authors.lastname: Choi
authors.forename: Hee-Yoon
authors.initials: HY
authors.lastname: Lee
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Hong
authors.forename: Myung Sook
authors.initials: MS
authors.lastname: Kim
authors.forename: Ky-Youb
authors.initials: KY
authors.lastname: Nam
authors.forename: Gyoonhee
authors.initials: G
authors.lastname: Han
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors; D000072198:ADAM17 Protein; D003374:Coumarins; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D003374:Coumarins; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein