Podophyllotoxin analogues active versus Trypanosoma brucei

Md Jashim Uddin, David C. Smithson, Kristin M. Brown, Brenda C. Crews, Michele Connelly, Fangyi Zhu, Lawrence J. Marnett, R. Kiplin Guy

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


In an effort to discover novel anti-trypanosomal compounds, a series of podophyllotoxin analogues coupled to non-steroidal anti-inflammatory drugs (NSAIDs) has been synthesized and evaluated for activity versus Trypanosoma brucei and a panel of human cell lines, revealing compounds with low nano-molar potencies. It was discovered that coupling of NSAIDs to podophyllotoxin increased the potencies of both compounds over 1300-fold. The compounds were shown to be cytostatic in nature and seem to act via de-polymerization of tubulin in a manner consistent with the known activities of podophyllotoxin. The potencies against T. brucei correlated directly with Log P values of the compounds, suggesting that the conjugates are acting as hydrophobic tags allowing podophyllotoxin to enter the cell.

Original languageEnglish
Pages (from-to)1787-1791
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Issue number5
StatePublished - Mar 1 2010

Bibliographical note

Funding Information:
We acknowledge support by the American Lebanese Syrian Associated Charities (ALSAC), St. Jude Children’s Research Hospital, and NIH Grant IU54CA105296 . We thank Dr. J. Pietenpol for the primary human mammary epithelial cells.


  • Microtubule
  • Sleeping sickness
  • Trypanosoma brucei

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


Dive into the research topics of 'Podophyllotoxin analogues active versus Trypanosoma brucei'. Together they form a unique fingerprint.

Cite this