title: Structure-activity relationships of N-benzylsalicylamides for inhibition of photosynthetic electron transport.
abstract: 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 μmol/L. Several evaluated compounds can be considered as effective PET inhibitors; these include N-(3,4- dichlorobenzyl)-2-hydroxy-5-nitrobenzamide (IC50 = 2.0 μmol/L), 3,5-dibromo-N-(3,4-dichlorobenzyl)-2-hydroxybenzamide (IC50 = 2.3 μmol/L) and 3,5-dibromo-N-(4-chlorobenzyl)-2-hydroxybenzamide (IC50 = 2.6 μmol/L) with activity comparable with that of the standard Diuron (IC50 = 1.9 μmol/L). The PET inhibiting activity increased approximately linearly with increasing lipophilicity of the compounds as well as with the increasing sum of Hammett σ 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 π; (1) and π(2)of individual substituents) and electronic properties of the substituents on the acyl (σ(1)) and the benzylamide fragments (σ(2)), the contribution of σ(1) being more significant than that of σ(2).
authors.forename: Katarina
authors.initials: K
authors.lastname: Kralova
authors.forename: Milan
authors.initials: M
authors.lastname: Perina
authors.forename: Karel
authors.initials: K
authors.lastname: Waisser
authors.affiliation: Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 612 42 Brno, Czech Republic. josef.jampilek@gmail.com.
authors.forename: Josef
authors.initials: J
authors.lastname: Jampilek
mesh_terms: D002736:Chloroplasts / Q000187:drug effects* / Q000378:metabolism; D015195:Drug Design; D004579:Electron Transport / Q000187:drug effects; D008956:Models, Chemical; D015394:Molecular Structure; D010788:Photosynthesis / Q000187:drug effects*; D021281:Quantitative Structure-Activity Relationship; D012457:Salicylamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018724:Spinacia oleracea / Q000187:drug effects* / Q000378:metabolism
chemical_list: D012457:Salicylamides