A QSAR study of acute toxicity of N-substituted fluoroacetamides to rats.
Acute toxicity in vivo toward rats, of nineteen N-alkyl and N-cycloalkyl fluorocetamides [F-CH(2)-C(O)-NH-R] was correlated with their structure-dependent properties. Used descriptors are: molecular weights (M(w)) and heat of formation (DeltaH(f)) of compounds; molar refractivity (CMR), lipophilicity (ClogP), Broto lipol values, virtual logP, molecular lipophilic potential (MLP), Van der Waals surfaces (VdW SAS) and hydropathicity surface (ILM) of whole molecules; Taft steric parameters (E(s)); E(s) values with Hancock corrections (E(s)(CH)) and Verloop sterimol (B(5)) and (L) parameters of alkyl and cycloalkyl residues; superdelocalizabilities and electron densities on the [NH-C(O)-CH(2)-F] fragment. Strong quantitative structure-activity relationships were assessed. Obtained correlation suggested that lipophilicity, shape and bulkiness of the alkyl and cycloalkyl substituents, particular nearest vicinity of the amide nitrogen, as well charges on the amide moiety are the main factors that influence on the acute toxicity of studied compounds toward rats. Mechanism of toxic action was proposed.
Juranić
Ivan O
IO
Faculty of Chemistry, University of Belgrade, P.O. Box 151, 11001 Belgrade, Serbia and Montenegro.
Drakulić
Branko J
BJ
Petrović
Slobodan D
SD
Mijin
Dusan Z
DZ
Stanković
Milena V
MV
D000818:Animals; D005463:Fluoroacetates / Q000737:chemistry / Q000633:toxicity*; D007928:Lethal Dose 50; D008297:Male; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D017208:Rats, Wistar
D005463:Fluoroacetates