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Structure‐activity relationships between antibacterial activities and physicochemical properties of sulfonamides
Author(s) -
Mengelers M.J.B.,
Hougee P.E.,
Janssen L.H.M.,
Van Miert A.S.J.P.A.M.
Publication year - 1997
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1046/j.1365-2885.1997.00063.x
Subject(s) - chemistry , acid dissociation constant , dissociation constant , antimicrobial , actinobacillus pleuropneumoniae , antibacterial activity , minimum inhibitory concentration , chromatography , organic chemistry , bacteria , biochemistry , aqueous solution , receptor , biology , genetics , gene
Relationships between the antimicrobial activities of sulfonamides and physico‐chemical properties including the acid dissociation constant (p K a ) and the hydrophobicity constant (π) were determined. The minimal inhibitory concentrations ( MIC ) of sulfonamides against Actinobacillus pleuropneumoniae , a gram‐negative veterinary pathogen, were used. High performance liquid chromatography was applied for the determination of the electronic and hydrophobic parameters. Empirically determined relationships pointed out the dominant role of the degree of ionization on the antimicrobial activity. The data indicate that hydrophobic properties of sulfonamides, characterized by π, are of minor importance for the in vitro antibacterial activity. Because of the restricted p K a range (4.9–7.7) it could not be established whether the relationship between pK a and activity was linear or bilinear. Whenever o,m ‐disubstituted sulfonamides were included correlations decreased substantially. Relationships based on multicompartment equilibrium models were derived and indicated a bilinear relation between p K a and MIC . Model‐based equations showed that the antibacterial activity was governed by the extracellular ionic concentration of the sulfonamides whenever different intra and extracellular pH values were assumed in the equilibrium model. The antimicrobial activities of the sulfonamides against gram‐positive organisms were also related to the degree of ionization of the sulfonamides in the agar medium.