Design,Synthesis And Antibacterial Activity Of Novel Tetrahydrocarbazole Derivatives

Antimicrobial Resistance(AMR)is the ability that bacteria can resist the effects of drugs.Bacterial resistance is generally divided into intrinsic resistance and acquired resistance(the leading cause of bacterial resistance).Acquired resistance includes resistance gene transfection and amplification,mutation of antibiotic targets,increased drug efflux or reduced drug absorption caused by bacterial cell membrane penetration Changes,antibiotics are modified by enzymes to render them inactive.Bacterial resistance as a role of defense mechanism for pathogen is always a constant induced by antibacterials.It is estimated that the number of deaths caused by drug-resistant infections in 2050 will reach 10 million people,resulting in global economic losses of$1 trillion if action is not taken.In recent years,the number of antibiotics approved by FDA decreased year by year,especially,antibiotics used for the treatment of Gram-negative bacterial infections are scarce,so it has great significance to develop new antibiotics.Our previous research indicated that 6-methyl-N-(4-phenylbutyl)-2,3,4,9-tetrahydro-lH-carbazol-1-amine possessed potential activity against Staphylococcus aureus Newman strain and multidrug-resistant strains(NRS-1,NRS-70,NRS-100,NRS-108 and NRS-271).Meanwhile we found that 2,4-diaminopyrimidine is a dominant group in antibacterial,we combined this group with the lead compound and synthesized a series of novel tetrahydrocarbazole derivatives and investigated their antibacterial activity.The results showed that G1 was the most potent compound which exhibited strong activity against S.aureus strain Newman,and multidrug-resistant S.aureus NRS-1,NRS-70,NRS-100,NRS-108 and NRS-271;and it could also inhibit E.coli AB1157,DH5a effectively with MIC values of 0.78-1.56 ?g/mL.