Studies On Synthesis. Activity Of Quinolone C-3[1,2,4] Triazole Sulfide And Derivatives (Ⅱ)： Levofloxactn And Ofloxacin Triazole Sulfide And Derivatives

With the acceleration of social urbanization and industrialization process, environmental pollutantsand the new chemical substances are increasing all the time. Combined with the impact of unhealthylifestyles and behavior, malignant cancer has become the number one killer of human health. Althoughthere are a large number of anticancer drugs continuously listed, efficacy of these drugs has always beennot recognized due to poor selectivity and ease of anticancer drugs tolerability. Therefore, researching anddeveloping of the new structure of the anti-cancer lead compounds becomes a major challenging issue inthe field of pharmaceutical chemistry and of great significance. The mechanism of quinolones onanti-tumor is similar with sterilization mechanism. The targets of these drugs in the cells are two kinds ofDNA topoisomerases: DNA gyrase and topoisomerase IV. According to this principle, Scientists havesynthesized a large number of antitumor quinolones compounds.At present, people focus on the structural modification of the quinolone compounds are concentratedin the N-1and C-7of the quinoline ring, there are less structural modification in Other location. But thesedrugs failed to enter clinical evaluation because of low bioavailability, In vivo toxicity and the body is easyto metabolic inactivation.In order to find effective ways of structural modification of antibacterial quinolone to thetransformation of the antitumor quinolone and get a certain anti-tumor activity of new quinolones, we usethe electronic isostere of heterocyclic or fused heterocyclic to replace the C-3position.1. Design and synthesis of target compoundsIn this paper, we use biological isostere and activity of splicing design principle to design andsynthetize26new compounds with ofloxacin and levofloxacin, and get the correspondingly targetcompounds. C-3carboxyl-bit of quinoline ring has been insteaded by triazole sulfide orthiazolo[3,2-b][1,2,4] triazole. The structures of new compounds syn-thesized had been characterized byMS、1H-NMR and IR. 2. Evaluation of antitumor activity in vitroThe inhibitory activity in vitro of cancer cell against A549cells, Bel-7402cells and HCT-8cells hasbeen evaluated by MTT assay respectively. The results show that the target compounds triazole sulfide andthiazolo [3,2-b][1,2,4] triazole have potential growth inhibitory activity on A549cells, Bel-7402cells andHCT-8cells3. ConclusionStructures of21target compounds were confirmed by spe-ctral data, the results of antitumor activityin vitro show that:10,12和21have very good growth inhibitory activity on A549cells and HCT-8cells.Therefore, quinolone C-3carboxylic is not necessary groups for antitumor activity, the modified structuresin the quinolone C-3carboxylic maybe developed into poten-tial anticancer drugs.