Study On Synthesis And Biological Activity Of Natural Substituted Cinnamaldehydes And Thiosemicarbazone Derivatives

Tyrosinase (EC.1.14.18.1) is a copper-containing enzyme widely distributed in microorganisms,animals and plants,which is of the activity of monophenolase and diphenolase.It is the rate-limiting enzyme in the synthesis of melanin organisms.Its inhibitors can be used widely in many fields including the preservation of fruits,vegetables and insecticide.Cinnamaldehyde is the main component of the natural lauraceae cinnamon, which shows many bioactivities in current research, such as vasodilator, anti-bacterial, antifungal anti-tumor activities and so on, and low toxicity. Thiosemicarbazone compounds formed by condensation of aldehyde or ketone compounds with amino thiourea also have wide biological activity.Cinnamaldehyde, o-methoxycinnamaldehyde,4-hydroxy-3-methoxycinnamaldehyde p-methoxycinnamaldehyde, o-hydroxycinnamaldehyde, p-hydroxycinnamaldehyde, synthesized in this paper and then we choosed ethanol and water as solvent, acetic acid as catalyst,thiosemicarzones compounds G-L were successfully synthesized,and their chemical structures were elucidated by 1HNMR.We studied the inhibitory effects of these coupunds on the activity of mushroom tyrosinase, spodoptera exigua phenoloxidase. The antibacterial effect of the synthesized compounds were also investigated with escherichia coli, bacillus subtilis and saccharomyces cerevisiae as test bacterias.Finally we did the mouse acute toxicity test with cinnamaldehyde thiosemicarbazone. The results are as follows:In the study of the impact on the monophenolase activity of mushroom tyrosinase, the results show that all the compounds have inhibitory activity, however in the activity study of diphenolase of mushroom tyrosinase, o-hydroxycinnamaldehyde, o-methoxycinnamaldehyde,4-hydroxy-3-methoxycinnamaldehyde activate mushroom tyrosinase. The o-hydroxycinnamaldehyde shows the strongest capability of activiation. Thiosemicarbazone compounds G-L can inhibit the diphenolase of mushroom tyrosinase, the IC50 are 7.1,6.1,5.2,4.6,3.5,12.1uM. The inhibitory mechanism of thiosemicarbazone compounds G-L are mixed type.In the activity study of diphenolase of spodoptera exigua phenol oxidase, the thiosemicarbazone compounds have inhibitory activity, the IC50 of thiosemicarbazone compounds G-L are 11.2,8.6,7.4,10.5,5.5,15.7uM.The antibacterial activity of the target compounds on Escherichia coli, Bacillus subtilis, Saccharomyces cerevisiae were tested with agar diffusion method. Compounds in the 200 mg/L showed some degree of inhibition; Compounds in the 600mg/L showed significant inhibition. Thiosemicarbazone compounds possessed more significant antibacterial activity. Selection of cinnamaldehyde thiosemicarbazone as representative determining LD50 with the mouse acute toxicity test. The results suggest that toxic of cinnamaldehyde thiosemicarbazone is weak.