Synthesis And Activities Of Metronidazole/Piperazine Derivatives Bridged By Five-membered Nitrogen Heterocycles

The five-membered nitrogen heterocyclic ring has a wide range of applications in fluorescent probes,medicines,materials,and other fields,Combining the research we did before,we modified the nitrogen heterocyclic ring,and explored its biological activity in antibacterial,inhibition of urease,and anti-inflammatory.The main research of the work is as follows:25 compounds were synthesized based on reaction of 1,2,4-triazole with metronidazole and 25 derieves were synthesized.These compounds were characterized by hydrogen spectroscopy,mass spectrometry and elemental analysis.The antibacterial activities show that these compounds have different degrees of inhibition on Staphylococcus aureus,Escherichia coli,Bacillus subtilis,Proteus.Since the N atom on the nitrogen heterocyclic ring has an electron donating ability and can coordinate with the metal ion,we introduce 2-pyridyl group to the 3 position of 1,2,4-triazole and the 2 position of 1,3,4-oxadiazole.Therefore B19 and B26 were synthesized.Reaction of B19 and B26 with Ag（Ⅰ）and Cu（Ⅱ）,we obtained 7 novel complexes.The activity of urease inhibition of these complexes were tested and the result showed that the IC₅₀s of all complexes were between 0.708±0.135?1.023±0.075μM which were better than the reference of AHA IC₅₀=8.881±0.688μM.The binding experiments of serum albiums were performed on all the complexes.The result showed that all the complexes had a static quenching effect on serum albumins and they had proper binding constants which could not only properly bind with albumins but also released from them,of these C7 had the highest quenching constant for the two albumins.Docking results showed that C3 tended to bind with the Model 1（Trp 134）.We also obtained piperazine derives based on 1,3,4-oxadiazole and they were characterized by HNMR,MS and elemental analysis.The in vivo anti-inflammatory activities of target compounds were evaluated by using classical para-xylene induced mice ear-swelling model.The in vivo anti-inflammatory assays indicated that most of the target compounds showed significant anti-inflammatory activities.Especially,compound H1 exhibited the most potent anti-inflammatory activity in vivo and did not cause gastric ulceration.