Abstract
3-O-3'(or 2')-Methylsuccinyl-betulinic acid (MSB) derivatives were separated by using recycle HPLC. The structures of four isomers were assigned by NMR and asymmetric synthesis. 3-O-3'S-Methylsuccinyl-betulinic acid (3'S-MSB, 4) exhibited potent anti-HIV activity with an EC(50) value of 0.0087microM and a TI value of 6.3x10(3), which is comparable to the data for bevirimat (DSB, PA-457), a current clinical trials drug that was also derived from betulinic acid. The anti-HIV potency of 4 was slightly better than that of AZT.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
MeSH terms
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Acquired Immunodeficiency Syndrome / drug therapy*
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Anti-HIV Agents / chemical synthesis*
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Anti-HIV Agents / pharmacology
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Cell Line, Tumor
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HIV-1 / drug effects
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HIV-1 / physiology
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Humans
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Stereoisomerism
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Structure-Activity Relationship
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Succinates / chemical synthesis*
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Succinates / pharmacology
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Triterpenes / chemical synthesis*
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Triterpenes / pharmacology
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Virus Replication / drug effects
Substances
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Anti-HIV Agents
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Succinates
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Triterpenes
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bevirimat