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In silico and in vitro genotoxicity evaluation of descarboxyl levofloxacin,an impurity in levofloxacin

中国药理学与毒理学杂志 2013年第3期 470-471页

作者： ZHU Qing-fen WEI Xi QU Jian-song LI Jun WANG Wei-jian Shandong Institute for Food and Drug Control

OBJECTIVE To evaluate the genotoxicity of descarboxyl levofloxacin by In silico and In vitro *** Assessment of genotoxicity using Derek for Windows We used DEREK for Windows(DfW,Lhasa Ltd.,Leeds,UK) version 11.0 for toxicity *** structures are entered into the program in *** *** program applies structure-activity relationships 〔(Q) SARs〕and other expert knowledge rules to derive a reasoned prediction about the potential toxicity of the query *** reverse mutation assay(Ames test) The Salmonella histidine point mutation assay proposed by Maron and Ameswas *** *** histidine autotrophic strains(TA97,TA98,TA100 and TA102) used in this test were obtained from Shandong center for disease *** saline(NS) was used as a vehicle control.2-Aminofluorene(2-AF,10 μg /plate),1,8-dihydroxyanthraquinone(50 μg /plate),Sodium azide(NaN3,1.5 μg /plate),and Dexon(50 μg /plate) were used as positive *** levofloxacin was assayed at concentrations of 31.25,62.5,125,250,and 500 μg /***,0.1 ml of test substance(or control solution),0.1 ml of bacterial culture 〔(1-2) × 1012 L-1 〕and 0.5 ml of S9 mix(NS for treatment without activation) were mixed and poured onto the agar plates after addition of 1.8 ml of top agar(0.6% agar Difco,0.5% NaCl,50 μmol·L-1 L-histidine,50 μmol·L-1 biotin,45℃) at 45℃.Plates were inverted and incubated for 48h at 37℃ in the *** colonies were counted and the background lawn was inspected for signs of toxicity or compound *** assay was performed two times in triple and included negative and positive *** al aberrations in Chinese ham ster lung cells Chinese Hamster Lung(CHL) cells were obtained from Shandong center for disease *** cells were grown in DMEM medium supplemented with 10% heat-inactivated calf serum at 37℃ in an atmosphere containing 5% of *** test for Chromosomal aberrations in CHL cells was con

关键词： genotoxicity impurity descarboxyl levofloxacin SARs CHL chromosomal aberration

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In silico and in vitro genotoxicity evaluation of descarboxyl levofloxacin,an impurity in levofloxacin

In silico and in vitro genotoxicity evaluation of descarboxy...

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2013年（第三届）中国药物毒理学年会暨药物非临床安全性评价研究论坛

作者： ZHU Qing-fen WEI Xia QU Jian-song LI Jun WANG Wei-jian Shandong Institute for Food and Drug Control

OBJECTIVE To evaluate the genotoxicity of descarboxyl levofloxacin by In silico and In vitro methods. METHODS Assessment of genotoxicity using Derek for Windows We used DEREK for Windows(DfW,Lhasa Ltd.,Leeds,UK) version 11.0 for toxicity *** structures are entered into the program in *** format. The program applies structure-activity relationships[(Q)SARs]and other expert knowledge rules to derive a reasoned prediction about the potential toxicity of the query *** reverse mutation assay(Ames test) The Salmonella histidine point mutation assay proposed by Maron and Ameswas *** *** histidine autotrophic strains(TA97,TA98,TA100 and TA102) used in this test were obtained from Shandong center for disease control. Normal saline(NS) was used as a vehicle control.2-Aminofluorene(2-AF,10μg/plate),1,8-dihydroxyanthraquinone (50μg/plate),Sodium azide(NaN,1.5μg/plate),and Dexon(50μg/plate) were used as positive *** levofloxacin was assayed at concentrations of 31.25,62.5,125,250,and 500 ug/***,0.1 ml of test substance(or control solution),0.1 ml of bacterial culture[(1 -2)×10L]and 0.5 ml of S9 mix(NS for treatment without activation) were mixed and poured onto the agar plates after addition of 1.8 ml of top agar(0.6%agar Difco, 0.5%NaCI,50μmol·L L-histidine,50μmol·L biotin,45℃at 45℃.Plates were inverted and incubated for 48h at 37℃in the *** colonies were counted and the background lawn was inspected for signs of toxicity or compound *** assay was performed two times in triple and included negative and positive *** aberrations in Chinese hamster lung cells Chinese Hamster Lung(CHL) cells were obtained from Shandong center for disease *** cells were grown in DMEM medium supplemented with 10%heat-inactivated calf serum at 37℃in an atmosphere containing 5%of *** test for Chromosomal aberrations in CHL cells was conducted according to published pr

关键词： genotoxicity impurity descarboxyl levofloxacin SARs CHL chromosomal aberration

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