| Literature DB >> 20129783 |
Md Jashim Uddin1, David C Smithson, Kristin M Brown, Brenda C Crews, Michele Connelly, Fangyi Zhu, Lawrence J Marnett, R Kiplin Guy.
Abstract
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 LogP values of the compounds, suggesting that the conjugates are acting as hydrophobic tags allowing podophyllotoxin to enter the cell. Copyright 2010 Elsevier Ltd. All rights reserved.Entities:
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Year: 2010 PMID： 20129783 PMCID： PMC2826502 DOI： 10.1016/j.bmcl.2010.01.009
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823