Benzene-di-N-octylcarbamates as conformationally constrained phospholipase A2 inhibitors

Conformationally constrained 1,2-, 1,3-, and 1,4-benzene-di-N-octylcarbamates are potent reversible competitive inhibitors of Naja mocambique mocambique phospholipase A2 with the Ki values of 11, 4, and 15 μM, respectively. With the angle of 120o 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 A2 inhibition mechanism by the inhibitor is proposed.