Synthesis And Antibacterial Activity Of Imidazole Derivatives Containing 6-methylpyridine Structure

In the progress of clinical and preclinical research on antibiotics in 2020,the WHO pointed out that although people are increasingly aware of the serious threat of bacterial resistance to antibiotics,antibiotics urgently needed for clinical treatment have not been developed all over the world.Therefore,it is urgent to design and synthesize compounds with new skeleton structure and antibacterial activity.In the previous work of this research,we found that derivatives with imidazo[2,1-b][1,3,4]thiadiazole structure and imidazole moiety had good antibacterial activity.Therefore,in order to investigate whether the new compounds containing these structures also have good antibacterial activities,two series of 39 new imidazole derivatives containing 6-methylpyridine structures(35a–z and 37a–o)were designed and synthesized,and their antibacterial activities were tested.Of compounds 35a–z,more than half of the compounds showed moderate or strong antibacterial activity.For Gram-positive bacteria 4220,compound 35u(MIC =0.5 μg/m L)had the highest antibacterial activity,which was equivalent to positive control compound gatifloxacin(MIC = 0.5 μg/m L).For Gram-positive bacteria 209,compounds 35x(MIC = 1 μg/m L),35p(MIC = 1 μg/m L)and 35q(MIC = 1 μg/m L)showed the highest activity,which was twice that of gatifloxacin(MIC = 2 μg/m L).For Gram-negative bacteria 1924,compounds 35o(MIC = 1 μg/m L)and 35v(MIC =1 μg/m L)showed the highest activity,which was similar to gatifloxacin(MIC = 0.5μg/m L).For Gram-negative bacteria 2742,all compounds had no antibacterial activity.For multidrug-resistant Gram-positive bacteria 3167,compound 35s(MIC = 0.5μg/m L)showed the highest activity,which was 4 times higher than that of gatifloxacin(MIC = 0.5 μg/m L).For multidrug-resistant Gram-positive bacteria 3505,compounds 35c(MIC = 2 μg/m L)and 35p(MIC = 2 μg/m L)showed the highest activity,which was equivalent to gatifloxacin(MIC = 2 μg/m L).Among compounds 37a–o,more than half of the compounds also showed moderate or strong antibacterial activity.For Gram-positive bacteria 4220,compounds 37l(MIC = 1 μg/m L)and 37j(MIC = 1 μg/m L)showed the highest activity,which was similar to gatifloxacin(MIC = 0.5 μg/m L).For Gram-positive bacteria 209,compounds 37k(MIC = 2 μg/m L)and 37m(MIC = 2 μg/m L)showed the highest activity,which was equivalent to gatifloxacin(MIC = 2 μg/m L).For Gram-negative bacteria 1924,compound 37m(MIC = 1 μg/m L)showed the highest activity,which was similar to gatifloxacin(MIC = 0.5 μg/m L).For Gram-negative bacteria 2742,all compounds had no antibacterial activity.For multidrug resistant Gram-positive bacteria 3767,compound 37e(MIC = 1 μg/m L)showed the highest activity,which was twice that of gatifloxacin(MIC = 2 μg/m L).For multidrug-resistant Gram-positive bacteria 3505,compound 37j(MIC = 2 μg/m L)showed the highest activity,which was equivalent to gatifloxacin(MIC = 2 μg/m L).In the previous research of our laboratory,the researchers obtained a series of compounds with strong bacteriostatic ability to fungi by introducing branched chains into the imidazole ring of the compound skeleton.These compounds have high selectivity to fungi and do not have broad-spectrum antifungal activity;In this study,a good broad-spectrum antibacterial activity was obtained by directly connecting the imidazole ring of the compound skeleton with the benzene ring or aromatic heterocycle.Among them,compounds 35 q,35t and 37 e had particularly obvious antibacterial effect on Gram-positive bacteria and multidrug-resistant Gram-positive bacteria.This study provides a method and theoretical basis for the design and optimization of such antibiotics.