Studies On C-3/C-6 Schiff Base Derivatives And Antitumor Activity Of Levofloxacin Analogues

At present, Tumor especially the malignant tumor has become one of diseases which seriously threat to human health. The development of anticancer drugs has become a challenging and significant issue in the field of life sciences. Fluoroquinolones which contain 4-quinolone scaffold are synthetic antibacterial agents with broad spectrum of activity. The target of quinolones is DNA topoisomerase II, the nature of which is similar to some anticancer drugs. So, based on such target to design and synthesis new antitumor quinolones has become a new strategy. Now, many studies have been reported. However, the structure modifications of fluoroquinolones are mainly related to N-1 and C-7 position of quinolone scaffold, where as few modifications for C-3 and C-6 position are reported, especially on the C-6 position of quinolone scaffold. Unfortunately, there are also have some problems, such as toxicity in vivo,low bioavailability in clinical. On the basis of the schiff base derivatives have a wide range of applications in antivirus and antitumor. We expect to synthesis the schiff base derivatives on the C-3 and C-6 position of fluoro- quinolones for development of new antitumor lead compounds derived from quinolones.1,Target compounds designIn this paper, 20 new compounds had been designed and synthesized with the precursor compound of Levofloxacin. Bioisosterism and combination of activity were the basic theories of drugs design. Two series of derivatives were obtained: one was the single schiff base derivatives on the C-3 position; the other was the double schiff base derivatives on the C-3 and C-6 position. The structures of new compounds syn- thesized had been characterized by MS,1H-NMR and IR.2,In vitro anticancer activity evaluationThe anticancer activity in vitro against MCF-7 cell line had been evaluated by MTT assay respectively, the bioactive assay showed that most new compounds exhibited a significant antitumor activity, especially the double schiff base derivatives.3,Conclusion The structures of new compounds synthesized are consistent with spectral data(10 single schiff base derivatives; 10 double schiff base derivatives). The bioactive in vitro assay shows that C₃-COOH and C6-F are not the necessary groups for antitumor activity of fluoroquinolones, the structural modifications of C₃-COOH and C6-F are meaningful, especially to the C-6 position.