Synthesis And Antibacterial Activities Research Of Glucosides Of1,2,4-triazoles

1,2,4-Triazoles nucleus and their derivatives have emerged rapidly because of good affinity towards pathogeny targets of HIV-RT and FabI, promising a variety of medical applications such as antibacterial, antifungal, antiviral and analgesic properties. Schiff base compounds have not only good coordination ability but also good anticancer, antibacterial, antiviral and other activity. It is known that carbohydrates and their derivatives have a significant biological role and occur widely in all living matter and function even appear to be essential to the process of infection by certain pathogenic species. Therefor, a series of3-S-β-D-glucosides-4-arylideneamino-5-aryl-1,2,4-triazoles(Al-A12),2-N-2’,3’,4’,6’-tetra-O-acetyl-β-D-glucopyranosyl-4-(N-substituted-phenyl)imino-5-methyl-1,2,4-triazoles(B1-B5) and2-N-2’,3’,4’,6’-tetra-O-acetyl-β-D-glucopyranosyl-4-(N-substituted-phenyl)imino-5-methyl-1,2,4-triazoles(C1-C5) were rationally designed and synthesized according to the principle of superposition of bioactive substructures by the combination of1,2,4-triazole, schiff base and glucosides.Firstly, substituted methyl benzoate were used as starting materitals to prepare the target compounds3-S-β-D-glucosides-4-arylideneamino-5-aryl-1,2,4-triazoles (A1-A12) by hydrazinolysis,salify,cycliztion and condensation. Secondly, compounds2-N-2’,3’,4’,6’-tetra-O-acetyl-β-D-glucopyranosyl-4-(N-substituted-phenyl)imino-5-methyl-1,2,4-triazoles(B1-B5) were obtained by a cyclization reaction of glacial acetic acid and thiocarbohydrazide, the condensation of substituted salicyladehyde and nucleophilic substitution reaction of intermediate and2’,3’,4’,6’-tetra-O-acetyl-a-D-glucopyranosyl. The former intermediate Schiff base were reducting by NaBH4. Then compounds2-N-2’,3’,4’,6’-tetra-O-acetyl-β-D-glucopyranosyl-4-(N-substituted-phenyl)imino-5-methyl-1,2,4-triazoles(C1～C5) were obtainer by nucleophilic substitution reaction of bromoacetyl glucopyranose and reduzate.The in vitro antimicrobial activity data showed that most of the tested compounds displayed good antimicrobial activities against Staphylococcus aureus (S.a.)(ATCC6538), Escherichia coli (E.c.)(ATCC8099) as well as Monilia albican (Ma.)(ATCC10231). Compounds A2、A5、A10、B2、B5、C2showed excellent activity against Escherichia coli, which were more effective than the reference drug fluconazole. Especially, compounds A2、 A10and C2exhibited broad spectrum antimicrobial activity with minimum values of MIC to all the three strains.Most of the compounds displayed better antifungal activity than antibacterial activity.The structure activity relationship of the synthesized compounds showed that halogen substituents increased the antibacterial activity. To compare the antimicrobial activity of the bromine and chlorine moiety on the phenyl ring, introduction bromine is more conducive to increase the antimicrobial activity. The introduction of glycosyl improved the biological activity of these compounds to against bacteria. The impact of the substituted group on the5of trizole is not obvious.