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Updated: May 9, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Synthesis and structure-activity relationship of 8-substituted protoberberine derivatives as a novel class of
Ying-Hong Li1, Hai-Gen Fu, Feng Su
1Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. lionking_0421@hotmail.com.
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.
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