Betulinic acid is a naturally occurring pentacyclic triterpenoid that has several important biological activities including the inhibition of HIV viruses. This compound can be found in many plants such as birch bark. This compound has low toxicity due to its natural origin, but its application has been hampered by its low solubility in water and organic solvents. Therefore, many derivatives of betulinic acid have been synthesized to improve its biological functions including serving as potent and highly selective inhibitors of HIV-1. In this study, we have prepared derivatives of betulinic acid by conjugating it with an amino acid, followed by complexing the conjugate with organic cations to form ionic salts. We hypothesize the incorporation of an amino acid and the formation of an ionic compound will greatly improve the solubility of betulinic acid in water and organic solvents, which will then enhance the anti-HIV activity of betulinic acid. After the preparation of novel ionic salts of betulinic acid, the derivatives were evaluated for inhibiting the activities of HIV-1 protease. HIV-1 protease is a retroviral aspartyl protease that is essential to the maturation of HIV viruses, and thus the inhibition of protease disrupts the HIV's ability to replicate and infect additional cells. Using the HIV-1 protease-catalyzed peptide hydrolysis assay as monitored by the HPLC analysis, we have achieved some preliminary successes, which suggest that new ionic derivatives of betulinic acid are more inhibitory to the HIV-1 protease activity than betulinic acid itself.

Preparing new betulinic acid derivatives for fighting HIV viruses

242nd National Meeting (2011)

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