Synthesis And Antibacterial Activities Research Of N-aryl-2-acetylamine-substituted 1,2,4-triazoles

1,2,4-triazole compounds which have less toxic to human cells are widely used in variousantibacterial, antiviral, anticancer and other drugs. Meanwhile, due to the presense of imidegroup, the Schiff base compounds have not only good coordination ability but also goodanticancer, antibacterial, antiviral and other activity. Therefore, the newcompounds-3-substituted sulfur-4-N-substituted (o-hydroxyl phenyl)imine- 5-alkyl-1,2,4-triazole have been synthesized based on rational combination of 1,2,4-triazoles,“-N=CH-“,o-hydroxydiphenyl ethers and“-NHCOCH2-”bridge group according to the excellentantibacterial activities of each segment and the superposition principle of reinforcement ofbiological activities. Furthermore, in order to improve heterocyclic compounds’in vivoabsorption, onset time and pharmacodynamics, 2-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)sulfur-5-(o-hydroxyphenyl)-1,3,4-oxadiazole (C) and 3-(2,3,4,6-tetra-O-acetyl-β-D- glucopyranosyl) sulfur-5-(o-hydroxy phenyl)-4H-1,2,4-triazole (D) have been synthesized byintroducing acetylglucose into different heterocyclic compounds.Firstly, the target compounds 3-(N-substituted phenyl-2-acetamido) sulfur-4- (N-substituted-2-hydroxyphenyl)imino-5-methyl-1,2,4-triazoles(A1~A20) and 3-(N-substitutedphenyl-2-acetamido)sulfur-4-(N-substituted-2-hydroxyphenyl) imino-5-ethyl- 1,2,4-triazoles(B1~B15) which have never been reported were synthesized by a cyclization reaction ofglacial acetic acid (or propionic acid) and thiocarbohydrazide, the condensation of substitutedsalicyladehyde and nucleophilic substitution reaction of intermediate and N-substitutedphenyl-2-acetamide. Secondly, 2,3,4,6-tetra-O-acetyl-α-D-bromo glucopyranose wassynthesized by the acylation and bromination of D-glucopyranose. Compound C and D weresynthesized high-selectivity by nucleophilic substitution reaction of bromoacetylglucopyranose and 5-(o-hydroxy phenyl) -1,3,4- oxadiazole-2-thione、5-(o-hydroxy phenyl)-4H-1,2,4- triazole-3-thione. The structures of all compounds have been confirmed by IR,1HNMR and13C NMR and the test of preliminary bioassay have been completed.The results of preliminary bioassay showed that, at the mass concentration of 10-4g/mL,the target compounds A1~A20、B1~B15 have strong inhibitory rate against Monilia albican,Staphylococcus aureus and Escherichia coli. Especially, the ratios of compound A5、A7 andA10 against Escherichia coli, compound A4、A8、A12 and A20 against Monilia albican areabove 100% as antigram-negative bacterial and antifungal agents respectively. The inhibitoryrate against Staphylococcus aureus of compounds A1~A20 are better than selling-drugfluconazole. The inhibitory rate against Monilia albican of compounds B1~B15 as a potentialantifungal agents are better than that against Staphylococcus aureus and Escherichia coli. Theinhibitory rate against Escherichia coli of compounds C and D are better than that againstStaphylococcus aureus and Monilia albican.The studies of structure-activity relationship show that the presence of halogen group in o-hydroxy phenyl ring can significantly increase the inhibitory rate. The substituent ofbenzene ring shows a significant influence on antibacterial activity; When substituent ismethyl group, the inhibitory rate against Monilia albican is better than others; Whensubstituent is nitro group, the inhibitory rate against Escherichia coli is better than others. Theinhibitory rate against all three strains are increased by the introduction of acetylglucopyranose. The inhibitory rate of compound D is better than that of compound C.