Journal of the Chemical Society Perkin Transactions 1 · 1975 · 32 citations · 0 references
PharmacyMedicinal ChemistryPharmacologyAntimicrobial PharmacologyMetabolismStructure-activity RelationshipsBiological MembranesDrug PermeationMechanisms Of Drug ActionQuantitative Structure-activity RelationshipsStructure-activity Relationship AnalysisAntibiotic Mechanisms Of ActionBiological Activity FeaturesChemical Structure-activity RelationshipsDrug - Membrane InteractionsIn Vivo StudiesMultiple RegressionSteric PropertiesSubstituent Effects On Biological Activity
The in vitro activity of a series of actinonin derivatives against S. aureus has been correlated with free-energy-related substituent parameters by multiple regression analysis. The activity shows a parabolic dependence on partition which probably reflects transport and membrane permeability factors. The relationships also show a dependence on the steric properties of the side-chains and it is suggested that biological activity may be associated with the formation of a tetrahedral transition state at the hydroxamic acid carbonyl group. In vivo activity is poor, possibly because of metabolism to inactive cleavage products.