Design,Synthesis And Biological Activity Evaluation Of Novel Guinoline And Benzothiazole Derivatives

Quinoline is a kind of N-containing heterocyclic compound,which is ubiquitous in nature and is the structural subunit of many natural products.Quinoline and its derivatives have a variety of biological activities,such as anti-tumor,antibacterial,anti-inflammatory,anti-virus,anti-malaria and so on.As a fused heterocyclic compound,benzothiazole derivatives have many biological activities,such as anti-tumor,anti-inflammatory,antibacterial,antiviral,antimalarial,anticonvulsant and so on.In recent years,a large number of quinoline and benzothiazole compounds with other active fragments have been synthesized by chemical methods,and their biological activities have been screened in vivo and in vitro.Some of them showed good anti-tumor activity,which laid the foundation for the development of new anti-tumor drug candidates.Therefore,in this paper,based on the molecular combination principle,the antitubulin polymerizetion inhibitory fragments such as 3,4,5-trimethoxyphenyl and triazole were introduced into quinoline and benzothiazole,and two series of new anti-tumor candidate compounds were synthesized.Finally,the compounds were structurally characterized and evaluated for their anti-tumor activity in vitro.the specific work is as follows:1.Using quinoline and benzothiazole as antitumor active fragments,the key fragments of tubulin polymerization inhibition,such as 3,4,5-tri-methoxyphenyl(TMP)and 1,2,3-triazole,were introduced based on the combination principle.35 novel quinoline derivatives containing benzoyl fragments and 26 novel benzothiazole triazole derivatives containing benzoyl fragments were synthesized,respectively.A total of 61 compounds were obtained in the two series,of which 60 target derivatives have not been reported,and the structures of the compounds were characterized by 1HNMR,13C NMR,HR-MS.2.MTT assay was used to evaluate the antitumor activity and structure-activity relationship of the synthesized compounds against human esophageal cancer cells(EC-109),human prostate cancer cells(PC-3)and human gastric cancer cells(MGC-803)in vitro.The results showed that the IC50 value of the most active compound in the new series of quinoline derivatives to MGC-803 cells at ?-3h was 1.89?M.Among the novel benzothiazole derivatives,compound ?-11j showed the best antitumor activity against EC-109,PC-3 and MGC-803,with IC50 values of 4.67?M,1.03?M and 0.047?M,respectively,which were significantly better than those of the positive control drug 5-fluorouracil,and the two series of compounds showed high selectivity to MGC-803 cells.