Lipophilicity of teicoplanin antibiotics as assessed by reversed phase high-performance liquid chromatography: quantitative structure-property and structure-activity relationships.
Structure-lipophilicity relationships of a large series of 63-COX teicoplanin antibiotic derivatives were examined, by correlating their capacity factors (log kw), measured through reversed-phase high-performance liquid chromatography on Deltabond C8 stationary phase, with some computed molecular properties such as fragmental log P constants (pi x), molecular volumes (Vx) 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 kw are mainly related to changes in bulk (modelled by Vx) 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.
Altomare
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Dipartimento Farmacochimico, University of Bari, Italy.
Carotti
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A
Cellamare
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S
Carrieri
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A
Ciabatti
R
R
Malabarba
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A
D002851:Chromatography, High Pressure Liquid; D004926:Escherichia coli / Q000187:drug effects*; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D012015:Reference Standards; D013329:Structure-Activity Relationship; D017334:Teicoplanin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014867:Water / Q000737:chemistry / Q000378:metabolism
D014867:Water; D017334:Teicoplanin