Studies On Synthesis, Activity Of Fluoroquinolone Forylhydrazones

The history of quinolones begins in the early 1970s with the synthesis of nalidixicacid. Fluoroquinolones are a group of complete synthesized broad-spectrum antibioticswhich basic structure is 1,4-dihydro-4-oxo-3-quinoline carboxylic acid. These compoundsare synthesized from quinoline and piperazine. Ever since the mechanism ofDu-6859a action has been elucidated, designation and synthesis new pattern ofantitumor quinolone is becoming one of popular research areas. As yet, antitumorquinolone compounds have been already synthesized, including bicyclic-, tricyclic- andquadrcyclic- quinolone, because of parallel toxicity and activity, lower bioavailability,and easily metabolism inactivity, finding new type of antitumor quinolone is becominghot spot all over the world. Based on the existing structure activity relationship ofFluoroquinolone, in view of the modification of quinolone drugs are focused on thestructure of its C-1 and N-7 in the research, and the modification of C-3 position is notcomprehensive enough. We alternate the C-3 carboxyl of fluoroquinolone skeleton todiscuss the effection of the structural modification on antibacterial, antitumor activity,thus, the C-3 substituted antitumor fluoroquinolones are meaningful for further study.Part one : Target compounds designIn this paper, 20 new compounds have been designed and synthesized withOfloxacin and Levofloxacin. What we utilize drug design principles are bioisosterismand combination of activity in target compounds design. The structures of new compoundssynthesized have been characterized by 1H-NMR,MS and IR. Part two : studies on Bioactivity of Target Compounds2.1 In vitro Antibacterial activity evaluationBroth dilution method has been used to research if target compounds inhibited the growth of S.aureus (ATCC29213), E.coli (ATCC25922) and P.aeruginosa (ATCC2785) in vitro. The result shows that few compounds have inhibitory activity for the three types of bacterial, most of compounds have no activity.2.2 In vitro anticancer activity evaluationThe anticancer activity in vitro against HEP-3B and BEL-7402 cell lines has been evaluated by MTT assay respectively, the bioactive assay shows that most new com- pounds exhibit a significant antitumor activity.Part three : ConclusionThe structures of new compounds are consistent with spectral data. The in vitro bioactive assay shows that C-3 site of carboxy group is not a necessary group for antitumor activity of quinolones.