title: Synthesis and structure-activity relationship of 8-substituted protoberberine derivatives as a novel class of antitubercular agents.
abstract: BACKGROUND
  The emergence of multi-drug resistant tuberculosis (MDR-TB) has heightened the need for new chemical classes and innovative strategies to tackle TB infections. It is urgent to discover new classes of molecules without cross-resistance with currently used antimycobacterial drugs.
  
  
  RESULTS
  Eighteen new 8-substituted protoberberine derivatives were synthesized and evaluated for their anti-mycobacterial activities against Mycobacterium tuberculosis (M. tuberculosis) strain H37Rv. Among them, compound 7g was the most effective antitubercular agent with minimum inhibitory concentration (MIC) of 0.5 μg/mL. Moreover, it also afforded a potent antitubercular effect against clinically isolated MDR strains of M. tuberculosis with MICs ranging from 0.25 to 1.0 μg/mL, suggesting a novel mode of action.
  
  
  CONCLUSIONS
  The structure-activity relationship (SAR) analysis revealed that introduction of a substituent at the 8-position in pseudoprotoberberine, especially an n-decyl, could significantly enhance the anti-TB activity. We consider 8-n-decylberberines to be a novel family of anti-tubercular agents with an advantage of inhibiting MDR strains of M. tuberculosis.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. lionking_0421@hotmail.com.
authors.forename: Ying-Hong
authors.initials: YH
authors.lastname: Li
authors.forename: Hai-Gen
authors.initials: HG
authors.lastname: Fu
authors.forename: Feng
authors.initials: F
authors.lastname: Su
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Gao
authors.forename: Sheng
authors.initials: S
authors.lastname: Tang
authors.forename: Chong-Wen
authors.initials: CW
authors.lastname: Bi
authors.forename: Yu-Huan
authors.initials: YH
authors.lastname: Li
authors.forename: Yan-Xiang
authors.initials: YX
authors.lastname: Wang
authors.forename: Dan-Qing
authors.initials: DQ
authors.lastname: Song