title: Design, synthesis and evaluation of novel metalloproteinase inhibitors based on L-tyrosine scaffold.
abstract: A series of novel L-tyrosine derivatives were designed, synthesized and assayed for their inhibitory activities on matrix metalloproteinase 2 (MMP-2) and histone deacetylase 8 (HDAC-8). The results showed that these L-tyrosine derivatives exhibited inhibitory profiles against MMP-2 and HDAC-8. The compounds 6h (IC(50)=0.013 ± 0.001 μM) and 6j (IC(50)=0.017 ± 0.001 μM) were equal potent MMP-2 inhibitors to the positive control NNGH (IC(50)=0.014 ± 0.001 μM). As for HDAC-8 inhibition, some of the hydroxamate compounds, such as 6d (IC(50)=3.6 ± 0.2 μM) and 6c (IC(50)=5.8 ± 0.5 μM), were equal potent to the positive control SAHA (IC(50)=1.6 ± 0.1 μM). Structure-activity relationships were also briefly discussed.
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China. chengxianchao2000@yahoo.com.cn
authors.forename: Xian-Chao
authors.initials: XC
authors.lastname: Cheng
authors.forename: Run-Ling
authors.initials: RL
authors.lastname: Wang
authors.forename: Zhen-Ke
authors.initials: ZK
authors.lastname: Dong
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Yao-Yuan
authors.initials: YY
authors.lastname: Li
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Li
mesh_terms: D015195:Drug Design; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D012097:Repressor Proteins; D014443:Tyrosine; D020778:Matrix Metalloproteinase 2; C409470:HDAC8 protein, human; D006655:Histone Deacetylases