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September 2001
Vol. 4, No. 9, p 11.
news in brief
Perish the parasite
Infectious diseases such as tuberculosis, African trypanosomiasis, malaria, and Leishmaniasis are a major health concern, collectively claiming millions of lives every year and threatening many more. In addition, opportunistic infections caused by pathogens such as Microsporidia and Pneumocystis carinii are becoming more prevalent.

The drugs now used to treat many of these diseases have severe side effects, are painful to administer, and are becoming less potent because of increasing resistance in the parasites. The development of novel drugs is required to combat these microbial pathogens.

Alkylated polyamine analogues are a potential prospect for anti-infective therapy. Polyamines are absolutely required for normal cell growth and division but their cellular functions are still undefined. Alkylpolyamine analogues down-regulate polyamine biosynthetic enzymes, but they cannot replace natural polyamine function. In the presence of the analogue, cells become polyamine-depleted, which leads to growth inhibition and apoptosis.

In a recent study by Patrick Woster and colleagues at Detroit’s Wayne State University (Bioorg. Med. Chem. Lett. 1996, 6, 2765), (bis)alkylated polyamines containing a 3–7–3 carbon skeleton displayed antitrypanosomal effects in vitro. As an extension of this study, Wayne State researcher Yu Zou and colleagues describe the synthesis of second-generation compounds and the screening for their activity against trypanosomes and Microsporidia (Bioorg. Med. Chem. Lett. 2001, 11, 1613–1617). Several of these compounds inhibited trypanosome growth in vitro, and one (compound 24) was more effective than the trypanocide melarsen oxide. It was also toxic to parasites that were resistant to melarsen oxide.

chemical structures: Compound 24 and Melarsen oxide

The researchers assayed the compounds’ antimicrosporidial activity by studying their effect on Encephalitozoon cuniculi infection in vitro and in mice. All of the mice treated with alkylated polyamines survived the infection and showed no signs of microsporidia, as assayed by histological staining and polymerase chain reaction analysis.

This study shows the potential strength of alkylated polyamine analogues as future therapeutics against various infectious diseases.


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