Studies On Synthesis And Antitumor Activity Of Quinolones C-3Chalcone Analogues

The quinolones are a group of human synthesized broad-spectrum antibiotics which basic structure is1,4-dihydro-4-oxo-3-quinoline carboxylic acid. For fifty years development, they have become thehigh-performance, broad-specturm and harmfulless antibiotics. The antibiotic targets of quinolones areDNA topoisomeraseⅡand DNA topoisomerase Ⅳ, more research reveals that the DNA topoisomerase Ⅱis also the main inracellular target of many antitumor drugs. To synthesis the new anticancer quinolnes hasbecome a new hot spot. Now, the new research shows that the structure modifications concentrated in thequinoline ring N-1, C-2, C-3, C-6, C-7can successfully change its antibictic action into cytotoxic effectabout mammalian cell. Many new compounds show good potential anticancer activity, but there is still nota quinolone antitumor drug on the market. It is the main job of researchers to find a new way to modifystructure and synthesis more and more high-effect and harmfulless lead compounds for further research..1. Design and synthesis of target compoundsIn this paper,24new compounds have been designed and synthesis with Norfloxacin, Ciprofloxacin,Oflloxacin and Levofloxacin. Through Reduction, Decarboxylation and Claisen-Schmidt reaction withsome aromatic alcohols, obtaining some Quinolones C-3Chalcone analogues. The structures of thecompounds have been characterized by MS、1H-NMR and IR.2. Evaluation of antitumor activity in vitroThe anticancer activity in vitro against non-small-cell lung carcinoma cell A549, human liver cancercell Bel-7402and human colon carcinoma cell HCT-8have been evaluated by MTT assay respectivel. Theresults show that part of the compounds have potential growth inhibitory activity on the three human cancercells.3. Conclusion24target compounds have been synthesized and confirmed by spectral datas, the result of theantitumor activity shows that: at the density of5μg/ml, the inhibition ratio of most compounds is betterthan control articles (Ciprofloxacin, Levofloxacin). Some compounds have good activity, such as theinhibition ratio of compound12e to A549is42.23%; the inhibition ratio of compound6f to Bel-7402is76.90%; the inhibition ratio of compound13f,6b,6d,6f,12e to HCT-8is55.79%,55.48%,50.75%, 58.38%. Therefore, Quinolones C-3Chalcone analogues may have better antitumor activity, its mechanismneeds further investigation.