Benzene-di-N-octylcarbamates as conformationally constrained phospholipase A(2) inhibitors
Gialih Lin1, Yan-Fu Lin, Mei-Ting Hwang
1Department of Chemistry, National Chung-Hsing University, Taichung 402, Taiwan. gilin@dragon.nchu.edu.tw
Bioorganic & Medicinal Chemistry Letters
|January 27, 2004
Abstract:
Conformationally constrained 1,2-, 1,3-, and 1,4-benzene-di-N-octylcarbamates are potent reversible competitive inhibitors of Naja mocambique mocambique phospholipase A(2) with the K(i) values of 11, 4, and 15 microM, respectively. With the angle of 120(o) between two C(benzene)-O bonds, 1,3-benzene-di-N-octylcarbamate mimics the preferable eclipsed C(sn-2)-O/C(sn-3)-O conformer of phospholipid in the enzyme-phospholipid complex. Further, a three-step phospholipase A(2) inhibition mechanism by the inhibitor is proposed.
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