Castanospermine is a substance derived from the Australian chestnut or black bean tree Castanospermum australe, a tree which is on the verge of extinction.

In the test tube, castanospermine inhibits the production of HIV's envelope protein gp120. Virus particles that are produced in the presence of castanospermine are unable to bind onto the CD4 receptor on human cells.

Several synthetic versions of castanospermine have been produced for study, the most promising of which is called bucast and is also sometimes referred to as B-Cast, MDL 28,574A or its chemical name 6-0-butanoylcastanospermine.

Current use

Castanospermine is an unlicensed, experimental drug. In tests with mice castanospermine appeared to be more toxic than AZT (zidovudine, Retrovir). It inhibited gut enzymes, making it harder for the mice to digest complex carbohydrates such as rice and bread and resulting in weight loss and lethargy. It also caused low blood platelet levels. One set of researchers found that the drug did inhibit mouse retroviruses, while another group found little evidence of antiviral effects.

Bucast has been shown to be 60 times more active against HIV than castanospermine. Two large trials testing bucast on its own and in combination with AZT began in late 1995 in Germany and the United States. Bucast appears to be well-tolerated, with the most common side-effects being mild to moderate flatulence and diarrhoea.

Development of this compund is no longer being pursued.

Key research

Ruprecht (1989) reported that in mice castanospermine caused weight loss, lethargy and thrombocytopenia but had antiretroviral effects. Hollingshead (1992) reported that although castanospermine reduced splenomegaly in mice infected with Rauscher murine leukaemia virus it did not lower viral titres.

Sunkara (1989) reported that bucast inhibited syncytium formation by HIV-1 in vitro. No host cell toxicity was observed at concentrations up to 200g/ml, and no toxicity was observed when the compound was administered to mice for 2 weeks at 200mg/kg/day. Taylor (1991) reported that in vitro bucast was at least 50 times more active than Butyl-DNJ and less active but better tolerated in cell culture than ddC.

Taylor (1995) found that the combination of bucast with AZT, ddI, ddC, nevirapine or saquinavir was synergistic in vitro, especially in triple drug combinations.

References

Hollingshead MG et al. An ELISA system for evaluating antiretroviral activity against Rauscher murine leukemia virus. Antivir Res 18: 267-274, 1992.

Ruprecht RM et al. In vivo analysis of castanospermine, a candidate antiretroviral agent. J Acquir Immune Defic Syndr 2: 149-157, 1989.

Sunkara PS et al. Anti-HIV activity of castanospermine analogues. Lancet 1: 1206, 1989.

Taylor DL et al. 6-0-butanoylcastanospermine (MDL 28,574) inhibits glycoprotein processing and the growth of HIVs. AIDS 5: 693-698, 1991.

Taylor DL et al. Synergistic inhibition of human immunodeficiency virus tyep 1 in vitro by 6-0-butanoylcastanospermine (MDL 28,574) in combination with inhibitors of the virus-encoded reverse transcriptase or protease. Antivir Chem Chemother 6: 143-152, 1995.