Structure-Activity Relationships of N-benzylsalicylamides for Inhibition of Photosynthetic Electron Transport
Abstrakt
Inhibition of photosynthetic electron transport (PET) in spinach chloroplasts by sixty-one ring-substituted N-benzylsalicylamides was investigated. The inhibitory potency of the compounds expressed by IC50 value varied from 2.0 to 425.3 mu mol/L.
Several evaluated compounds can be considered as effective PET inhibitors; these include N-(3,4-dichlorobenzyl)-2-hydroxy-5-nitrobenzamide (IC50 = 2.0 mu mol/L), 3,5-dibromo-N-(3,4-dichlorobenzyl)-2-hydroxybenzamide (IC50 = 2.3 mu mol/L) and 3,5-dibromo-N-(4-chlorobenzyl)-2-hydroxybenzamide (IC50 = 2.6 mu mol/L) with activity comparable with that of the standard Diuron (IC50 = 1.9 mu mol/L). The PET inhibiting activity increased approximately linearly with increasing lipophilicity of the compounds as well as with the increasing sum of Hammett sigma constants of the substituents on the acyl fragment (R-1 = H, 5-OCH3, 5-CH3, 5-Cl, 5-Br, 5-NO2, 4-OCH3, 4-Cl, 3,5-Cl and 3,5-Br) and the benzylamide fragment (R-2 = H, 4-OCH3, 4-CH3, 4-F, 4-Cl and 3,4-Cl).
Based on the evaluated structure-PET inhibiting activity relationships (QSAR) it was confirmed that the inhibitory activity of the compounds depends on lipophilicity (log P or distributive parameters pi(1) and pi(2) of individual substituents) and electronic properties of the substituents on the acyl (sigma(1)) and the benzylamide fragments (sigma(2)), the contribution of sigma(1) being more significant than that of sigma(2).