Studies On Synthesis, Antibacterial Activity And Anticancer Activity Of Fluoroquinolone Forylhydrazones

The quinolones are a group of synthetic and containing 4 - methaqualone nucleus antibacterial agents. For its broad spectrum antimicrobial activity, fewer side effects, such as the unique features of the mechanism, widely used in clinical treatment of various infections, is the most important of a class of antibacterial drugs. However, the mechanism of drug resistance and further development of research has encountered numerous problems. Meanwhile, the topoisomerase-based design and development for the shift from an antibacterial to an antitumor have been a new strategy in the fluoroquinolone field. Based on the existing structure activity relationship of Fluoroquinolone, in view of the modification of quinolone drugs focused on the structure of its 1 - bit and 7 - bit in the research, and the modification of C-3 position is not comprehensive enough and in-depth, We alternate the fluoroquinolone skeleton C-3 carboxyl to hydrazone for hydrazone compounds were widely used in antibacter,antitumor,antivirus, and discuss the effaction of the structural modification on anti-bacterial, anti-tumor activity, thus, the C-3 hydrazone substituted antitumor fluoroquinolones are value for further study.Part one :Target compounds designIn this paper, 20 new compounds have been designed and synthesized with N-methyl-Ciprofloxacin,Enrofloxacin,7-Chloro-1 -cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,7-Chloro -1-cyclopropyl -6-fluoro -4-oxo -1,4-dihydro -quinoline-3-carboxylic acid ethyl ester as Lead compound and the basic theories of drug design, such as bioisosterism and combination of activity. The structures of new compounds synthesized were characterized by by 1H-NMR,MS and IR.Part two : studies on Bioactivity of Target Compounds2.1 In vitro Antibacterial activity evaluation Their in vitro antibacterial activity against the three bacteria cell lines of S.aureus (ATCC29213),E.coli (ATCC25922) and P.aeruginosa (ATCC2785) were evaluated by Broth dilution method. The results showed that most N-methyl-Ciprofloxacin hydrazone compounds and some 7-Chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro -quinoline-3-carboxylic acid ethyl ester hydrazone exhibited a significant antibacterial activity, others less.2.2 In vitro anticancer activity evaluationThe in vitro anticancer activity of N-methyl-Ciprofloxacin hydrazone against SGC-7901,Enrofloxacin hydrazone against BEL-7402 and the other compounds against SMMC-772 cell lines was evaluated by MTT assay respectively, the bioactive assay showed that most new compounds exhibited a significant antitumor activity.Part Three ConclusionThe structures of 20 new compounds synthesized were consistent with spectral data. The in vitro bioactive assay showed that 3- carboxy group is not a necessary group for antibacterial activity and antitumor activity of quinolones.