Structural Modification And Antibacterial Activity Evaluation Of Fluoroquinolones

Quinolone has a wide spectrum of antibacterial activity,which is favored by clinicians and researchers.However,with the widespread use of antibiotics,bacterial resistance continues to emerge,and it is necessary to find better antibacterials.This paper focuses on the structural modification of quinolones and the evaluation of antibacterial pharmacological activities.I.Synthesis,Characterization and Antibacterial Activity Evaluation of DOTA Modified QuinoloneTeichoic acid is one of the main components of the cell wall of Gram-positive bacteria,and its surface carries a large amount of negative charges,which can enrich metal ions around the cells.Mg2+ can inhibit the activity of bacterial synthetase,which can reduce bacterial growth.DOTA,as a metal ion chelating agent,has good water solubility and biocompatibility.Based on the DOTA modified drug molecules,the water solubility could be changed.Meanwhile,the concentration of drugs around the bacteria could be further increased by intermolecular hydrogen bonding and complexation coordination,which affected the viability of bacteria.Based on this consideration,we designed and synthesized 21 quinolone compounds,including 14 new chemical entity and 7 water-soluble DOTA modified compounds.The result of activity indicated that compound 4c has good antibacterial activity(MRSA,MIC:1.56 μg/mL;MBC:6.25 μg/mL),good water solubility and no cytotoxicity.Animal experiments showed that 4c was superior to clinical drug meropenem against MRS A activity in vivo.Ⅱ.Synthesis,Characterization and Antibacterial Activity Evaluation of Small Molecule Structure Modified BalofloxacinBased on the drug metabolism pathway(acetylation,methylation,amino acidization,etc.)and heterocyclic small molecule(triazole,furan,thiophene,etc.),xwe synthesized 22 small molecule quinolone compounds and passed HRMS,1H NMR,13C NMR structural characterization.The antibacterial activity results showed that the three compounds of 2-e,3-e,4-e were superior to the antibacterial activity of MRSA in balolloxacin.Especially,the antibacterial activity of compound 2-e was superior to balofloxacin against MRSA and P.aeruginosa(MRSA,MIC:0.0195 μg/mL,MBC:0.039 μg/mL,P.aeruginosa MIC:0.039 μg/mL,MBC:0.078 μg/mL),and had no obvious cytotoxicity and no hemolysis effect to red blood cells.Morphological studies had also shown that 2-e was good antibacterial hit for further study.Ⅲ.The Preliminary Exploration of Photodynamic Antibacterial of Quinolone DrugsThe quinolone compounds have photosensitizing side effects in clinical practice.We studied the photodynamics between MRSA,P.aeruginosa and E.coli by comparing the different light conditions of sparfloxacin(SPFX)and gatifloxacin(GFLX).As a result,the introduction of photodynamic means did not damage cells.To some extent,the antibacterial activity of GFLX and SPFX could be increased,but the lifting capacity was limited.So the quinolones are not effective photosensitizers,they are relatively safe antibacterial drugs in clinic.