Inhibition of DNA topoisomerase I by natural and synthetic mono- and dimeric protoberberine alkaloids

Yong Qin, Ji Yan Pang, Wen Hua Chen, Zhongzhen ZHAO, Liang LIU, Zhi Hong JIANG*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

50 Citations (Scopus)


A series of natural (i.e., 1-7) and synthetic (i.e., 8-23) protoberberine alkaloids were evaluated for their inhibitory activities towards DNA topoisomerase I. Both the natural, monomeric protoberberine alkaloids and their mono-modified congeners showed only minor activities. In contrast, most of the dimeric protoberberine alkaloids, especially compounds 12-22, were highly active, with a similar cleavage efficiency as camptothecin (CPT), a well-known, potent topoisomerase-I inhibitor. Thus, these dimeric compounds are promising candidates to be further elaborated as anticancer leads. The mechanism of topoisomerase-I inhibition seems to be dependent on drug concentration for the dimeric protoberberines. At low concentration, they exhibit similar characteristics as CPT. At high concentration, this ability is mostly lost, and the dimers inhibit the relaxation activity of topoisomerase I. Thus, we suppose that the active, dimeric protoberberines strongly bind to plasmid DNA at elevated drug concentration. This most likely results in blocking the enzyme's access to plasmid DNA, thus inhibiting its relaxation.

Original languageEnglish
Pages (from-to)481-487
Number of pages7
JournalChemistry and Biodiversity
Issue number3
Publication statusPublished - 2007

Scopus Subject Areas

  • Bioengineering
  • Biochemistry
  • Chemistry(all)
  • Molecular Medicine
  • Molecular Biology


Dive into the research topics of 'Inhibition of DNA topoisomerase I by natural and synthetic mono- and dimeric protoberberine alkaloids'. Together they form a unique fingerprint.

Cite this