Role of sulfonamide group in matrix metalloproteinase inhibitors.
Sulfonamide hydroxamates were designed and synthesized as efficient matrix metalloproteinase (MMP) inhibitors since the discovery of CGS 27023A in 1994. The sulfonamide group was incorporated in the inhibitor to improve the enzyme-inhibitor binding, not only by forming hydrogen bonds to the enzyme but also by properly directing the hydrophobic substituent to the S1' pocket and enabling it to plunge in deeply. Some researchers even presumed that the sulfonamide group, together with the zinc binding group (ZBG), coordinated the zinc ion within the MMP active site. This review will illustrate the role of the sulfonamide group in MMP inhibitors.
Cheng
Xian-Chao
XC
Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China. chengxianchao2000@yahoo.com.cn
Wang
Qiang
Q
Fang
Hao
H
Xu
Wen-Fang
WF
D000818:Animals; D001665:Binding Sites; D006801:Humans; D006860:Hydrogen Bonding; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000737:chemistry*; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*
D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D013449:Sulfonamides; D020782:Matrix Metalloproteinases