Studies On Synthesis, Activity Of Quinolone C-3"1, 3, 4" Triazole Sulfide And Derivatives

At present, the tumor disease has become the first killer to human health, although a large number of anticancer drugs continuously available, however the low selectivity and the easily tolerance cause they can not achieve satisfactory therapeutic effect. Therefore, the search for new anticancer lead compound structure has become the urgent problems to be solved of the field of medicinal chemistry. Quinolones are wide attenation with tumor chemists by its unique mechanism. The mechanism of anticancer drugs to kill cancer cells are similar with quinolone to kill bacteria, according to this principle, a large number of antitumor quinolones compounds have been synthesized, but because of the body toxicity, low bioavailability, easy deactivation in vivo, they are not enter into the clinical evaluation. The modified structure of the quinolone compounds concentrated in the quinoline ring N-1 and C-7, while the other positions have less studies. Some research have shown that the target objects of structural modification on the other positions have antitumor effect also, but, there is still not a quinolone antitumor drug on the market. Existing research results show that, C-3 bit carboxyl group is not necessary for antitumor activity, the position can be instead by some heterocyclic electronics. Therefore, may be we can get a better antitumor activity of quinolone compound by alternating the C-3 carboxyl with heterocyclic or fused heterocyclic, and, find the effective ways and means of the structural modification for the transformation of quinolone antibacterial to quinolone antitumor.1. Design and synthesis of target compoundsIn this paper, 24 new compounds have been designed and synthesis with Nor- floxacin and Cipro- floxacin. Quinoline ring C-3 carboxyl-bit has been insteaded by triazole sulfide or thiazolo[3,2-b][1,2,4] triazole, getting the correspondingly target compounds.2. Evaluation of antitumor activity in vitroThe inhibitory activity in vitro of cancer cell against human breast cancer cell MCF-7 has been evaluated by MTT assay respectively. The results show that the target compounds triazole sulfide and thiazolo [3,2-b][1,2,4] triazole have potential growth inhibitory activity on human breast cancer cells 3. Conclusion24 target compounds were synthesized and their structures confirmed by spectral data, the results of antitumor activity in vitro show that: in the 24 target com- pounds, the IC₅₀ of two compounds less than 10μM, the IC₅₀ of fifteen compounds are between in the 10μM and 50μM. The IC₅₀s of Compounds 6h,14b are 6.18μM, 2.63μM, show that they have very good growth inhibitory activity on the human breast cancer cell MCF-7. Therefore, quinolone C-3 carboxylic is not necessary groups for antitumor activity, the...