QSAR for phospholipase A2 inhibitions by 1-acyloxy-3-N-n-octylcarbamyl-benzenes

1-Acyloxy-3-N-n-octylcarbamyl-benzenes are potent reversible competitive inhibitors of Naja mocambique mocambique phospholipase A2 with the Ki values from 9.6 to 119 μM. The pKi values are correlated to both Taft substituent constant σ* and Hansch hydrophobicity constant π. The pre-steady state inhibition studies indicate that the pKS values for the first inhibition step are linearly correlated to σ* alone with the ρ* of −0.09 for this correlation. Thus, the first inhibition step may involve the insertion of the inhibitor to hepta-coordinated Ca2+ ion of the enzyme to form the octa-coordinated Ca2+ ion of the enzyme. The log(k2/k−2) values for the second inhibition step are linearly correlated to π alone, and the ψ value for this correlation is 0.13. Therefore, the second step inhibition step may involve the van der Waals’ interaction between the acyl group of the inhibitor and Tyr 69 of the enzyme.