Synthesis Of Dihydrothiazoles: In Vitro Antibacterial Activities And Preliminary Mechanism Of Action

Our country is a large agricultural nation, the plant bacterial disease has become one of the major diseases affecting agricultural production, seriously affected agricultural production and produced a huge economy loss. In 2012, A compound was isolated from a bacterium fermentation broth in the Pesticide Reasearch Institute, Northwest A&F University, and it was named Yanglingmycin. Yanglingmycin showed efficient antibacterial activities.In 2014, our group successfully synthesized Yanglingmycin and analogs. We evaulated their biological activities and found that the antibacterial activity of dihydrothiazoles exhibited more potent than Yanglingmycin. We want to reasearch the relationship between structure and biological activity of dihydrothiazoles, and to found the activiter compounds. We designed and synthesized 80 dihydrothiazoles, including 62 unknown compounds. We evaulated their biological activities against common bacterial pathogens. The results are as follows:(1) Cysteine and aromatic nitrile were used as raw materials. After literatures reviewd, we tried three methods to synthesize dihydrothiazoles. And perform NMR data, optical and melting point of all compounds were identified their structures.(2) Filter paper method to evaluate the inhibitory activity. Ampicillin as a positive control, determination of drug loading was 1μg, 80 compounds were evaluate the inhibitory activity. Including, Bacillus cereus, Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Pseudomonas syringae pv. actinidiae, Pseudomonas solanacearum, Ralstonia solanacearum. Especially 7h and 7h’ showed the most antibacterial activity for all experimental bacterias.(3) Minimum inhibitory concentration(MIC). Using the dilution method to determine the activity of the compound is preferably MIC, test results show that the activity of a series of hydroxyl o-substituted on the phenyl compounds showed different antibacteria activity, wherein the 7h and 7h ’showed better than the positive controls ampicillin resistant Bacillus subtilis and Pseudomonas syringae pv. actinidiae, which MICs were 7.81μg / m L and 3.91μg / m L.(4) Scanning electron microscopy. In view of the 7h and 7h’ showed such a strong antibacterial activity, in order to explore the mechanism of inhibition experiments done morphology, scanning electron microscope showed that the 7h act on the cell wall of Bacillus cereus, the cell wall is damaged, the cell contents logistics come out. This phenomenon and the role of cell wall Yanglingmycin similar.(5) Fatty acid exposure experiment. On the basis of the scanning electron microscope, we have to verify the effect of 7h fatty acid synthase in the cell wall, designed to add fatty acids experimental results show that after joining with the concentration of long chain fatty acids increases decreases inhibition zone, the Conclusion the experimental results have been highly Yanglingmycin.