Castanospermine vs. its 6-O-butanoyl analog: a comparison of toxicity and antiviral activity in vitro and in vivo

Article Abstract:

Glycoproteins are protein molecules that contain sugars. The protein portion of the molecules is synthesized first and the sugars are added at a later stage, known as processing. In tissue culture cells (which are grown outside of the body), drugs which inhibit the processing of glycoproteins have been shown to inhibit the human immunodeficiency virus type-1 (HIV-1), which contains glycoproteins. Yet these drugs have minimal toxic effects on the cells which contain the virus. Studies in mice infected with a type of retrovirus similar to HIV have shown that treatment with castanospermine, an inhibitor of glycoproteins, was less effective and more toxic than the standard treatment of zidovudine, the antiviral drug often used for HIV infection. A synthetic variant, the 6-O-butanoyl analog of castanospermine, was tested and had greater activity against infected cells grown in tissue culture than the parent compound. However, when tested in mice, the analog showed no advantage over the parent compound in antiviral effect or toxicity to the human cells. It is possible that the analog gets converted to the parent compound in the body. So although the compounds are active against HIV, castanospermine and its 6-O-butanoyl analog are not as effective a treatment as zidovudine. However, it is possible that these drugs could be used in combination therapies with zidovudine or other drugs. (Consumer Summary produced by Reliance Medical Information, Inc.)

Research, Glycoproteins, Alkaloids, Castanospermine

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Progressive CD4 cell depletion and death in zidovudine-treated patients

Article Abstract:

A CD4 T-cell count of less than 50 cells per cubic millimeter may increase the risk of life-threatening opportunistic infections in individuals with advanced HIV infection. Among 1,415 individuals with advanced HIV infection who were treated with zidovudine (AZT), 432 had died by Dec 1991. Only 26% of the patients survived two years after their T-cell count initially fell below 50 cells, compared to 51% after their T-cell count initially fell between 51 and 100 cells. Eighty-six percent of the patients had a T-cell count of less than 50 cells one month before death, compared with 58% one year before death and 33% two years before death. T-cell count should be monitored closely in patients in the advanced stages of HIV infection.

Health aspects, Physiological aspects, Zidovudine, CD4 lymphocytes

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