Structure‐activity relationships between antibacterial activities and physicochemical properties of sulfonamides

Abstract

Relationships between the antimicrobial activities of sulfonamides and physicochemical properties including the acid dissociation constant (pKa) and the hydrophobicity constant (pi) 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 pi, are of minor importance for the in vitro antibacterial activity. Because of the restricted pKa range (4.9-7.7) it could not be established whether the relationship between pKa 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 pKa 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.

Microbial inhibition by pharmaceutical antibiotics in different soils—dose-response relations determined with the iron(III) reduction test

“…The results indicate that the effective doses vary depending on the speciation and resulting polarity of the antibiotics. This corresponds with results from Mengelers et al [35], who reported that the antimicrobial activity of sulfonamides against gram-negative and gram-positive organisms was related to the degree of ionized and highly polar species in the agar medium.…”

Joint antibacterial activity of soil-adsorbed antibiotics trimethoprim and sulfamethazine

“…Consequently, the easier antibiotic desorbed, the stronger bioactivity exhibited. Mengelers et al (1997) observed that the degree of ionization plays the dominant role in antibacterial activity of sulfonamides. Thus, factors that influence ionization or sorption-desorption processes of an antibiotic are important in determining the antibiotic activity of the soil-adsorbed antibiotic.…”

Similarities and differences in combined toxicity of sulfonamides and other antibiotics towards bacteria for environmental risk assessment

“…Therefore, the difference on toxicity caused by individual antibiotics to different organisms may be related to not only antibiotics into cells but also antibiotics binding target receptor. Furthermore, the capacity of SAs into cell can be determined by the pKa value (Zarfl et al 2008) which is the decisive factor in transporting SAs into the cell (Mengelers et al 1997) while binding effect is quantified by using E binding (Cassee et al 1998). Zou et al (2012b) found that the toxicity of SAs in luminous bacteria showed a good linear relationship with the two parameters (pKa and E binding ); similar results were obtained in this study.…”