Anti-tuberculosis Active Ingredients And Structural Modification Of Honeysuckle And Honeysuckl

Tuberculosis(TB)is an infectious disease primarily transmitted through the air by the Mycobacterium tuberculosis(MTB)bacterium,which mainly infects the lungs.China is one of the high-burden countries for TB,and due to the increasing number of drug-resistant TB cases in recent years,there is an urgent need to discover new anti-TB molecules with novel mechanisms of action.This paper first compared the antimycobacterial activity of ethanolic extracts of Caulis Lonicerae and Lonicerae flos,and found that the activity of Lonicerae flos was stronger than that of Caulis Lonicerae.The active monomer was obtained from the active tracking and separation of the Caulis Lonicerae extract,and was identified as ferulic acid with an MIC value of 100 μg/m L.For the Lonicerae flos extract,due to its high polarity,the content of the active site decreased after separation.According to literature reports,the active antimycobacterial molecule in Lonicerae flos may be a purine compound.In order to obtain a more potent compound,three ferulic acid derivatives were synthesized,but their activity did not reach the expected target.The structure of the purine derivative after opening the ring was modified,and eight compounds were synthesized by combining with quinoline,among which compound 7 showed strong antimycobacterial activity(MIC=8 μg/m L).To explore the mechanism of action of compound 7 against Mycobacterium tuberculosis,molecular docking was first performed on the molecule.The results showed that compound 7 had strong affinity for Mycobacterium tuberculosis Kat G.Mycobacterium tuberculosis Kat G was purified using SDS-PAGE,and the enzyme inhibition results showed that compound 7 had an inhibitory effect on Kat G enzyme.In addition,the relative content of intracellular oxygen free radicals testing results showed that the higher the concentration of compound 7,the more intracellular oxygen free radicals accumulated.The morphology of the bacterial cells indicated that compound 7 caused damage to the cell wall of Mycobacterium tuberculosis.The research results of this paper show that ferulic acid is one of the main active components against Mycobacterium tuberculosis in Caulis Lonicerae,while purine compounds may be the main active components against Mycobacterium tuberculosis in Lonicerae flos,providing experimental basis for clinical application.Compound 7 was obtained through structure modification,and it has strong activity.The preliminary verification suggests that inhibiting Kat G enzyme may be its mechanism of action against Mycobacterium tuberculosis,providing new ideas for the synthesis of new antimycobacterial molecules with novel mechanisms of action.