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Syntheses and Biological Activities of New N 1 ‐Aryl Substituted Quinolone Antibacterials
Author(s) -
Jürgens Jens,
Schedletzky Holger,
Heisig Peter,
Seydel Joachim K.,
Wiedemann Bernd,
Holzgrabe Ulrike
Publication year - 1996
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19963290403
Subject(s) - lipophilicity , dna gyrase , chemistry , stereochemistry , dna supercoil , quinolone , quantitative structure–activity relationship , aryl , ring (chemistry) , antibacterial agent , dna , biological activity , in vitro , antibiotics , escherichia coli , biochemistry , organic chemistry , dna replication , gene , alkyl
A series of quinolones with a systematically varied substitution at the phenyl ring at N1 has been synthesized. Three lipophilicity descriptors (log K , log P, R m ) and the p K a values have been determined as well as the microbiological activity: The MIC values for eight different strains of three Gram‐positive and three Gram‐negative species and the inhibitory concentrations of DNA supercoiling (IC 90 and IC 100 ) were determined. From a principal component and a QSAR analysis relationships between the antibacterial activity concerning the whole‐cell system and electronic properties as well as the length of the substituents at the phenyl rings could be derived. The activity in a cell‐free system was governed by the lipophilicity and width of the substituents. It is speculated that the quinolones take a defined place in the DNA gyrase‐DNA complex which is characterized by polar amino acids. This is in agreement with findings from studies of mutant gyrases.