Lipophilicity of Teicoplanin Antibiotics as Assessed by Reversed Phase High-performance Liquid Chromatography: Quantitative Structure-property and Structure-activity Relationships

Abstract— Structure-lipophilicity relationships of a large series of 63-COX teicoplanin antibiotic derivatives were examined, by correlating their capacity factors (log k_w), measured through reversed-phase high-performance liquid chromatography on Deltabond C₈ stationary phase, with some computed molecular properties such as fragmental log P constants (***_x), molecular volumes (V_x) and factors imparting hydrophilicity (e.g. amino groups in the X chain, nN). A number of equations were derived which demonstrate that variations of log k_w are mainly related to changes in bulk (modelled by V_x) and polarity (primarily modelled by nN) of X chains of teicoplanin derivatives. QSAR analysis revealed that in-vitro activity against E. coli increases as lipophilicity decreases and isoelectric point increases.