Reduction of in vitro clastogenicity induced by the mixture of optical isomers of nadifloxacin during storage
1995
The fluoroquinolone antibacterial agent, nadifloxacin (NDFX, CAS 124858-35-1), is a racemic compound. The storage effect on the in vitro clastogenicity of a solution of the racemic compound and a mixture solution of the optical isomers of NDFX, prepared by mixing equal amounts of S- and R-enantiomers, was investigated. The potential of NDFX and the enantiomer mixture, prepared from equal amounts of each S- and R-enantiomer, to induce chromosomal aberrations in vitro was investigated in cultured fibroblasts derived from Chinese hamster lung cells immediately, 2 and 4 weeks after preparation of the test solutions (stored at 20 o C, protected from light) using 24 h of continuous treatment method. In the results, NDFX did not significantly increase the incidence of chromosomal aberrations at 200 μg/mL regardless of the storage period. On the other hand, the mixture significantly increased the incidence of chromosomal aberrations at 200 μg/ml immediately after preparation to an extent similar to that of S-enantiomer alone, but the mixture did not do so after 2 and 4 weeks of storage, Neither S- nor R-enantiomer changed the chromosomal aberration inducibility during storage. The content and optical purity of the test substances in each test solution also did not change during storage. These facts suggested that the molecular condition of each optical isomer in the mixture solution became equivalent to that in the racemic solution during storage periods
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