Abstract
We herein report a new compound: 10-chloromethyl-11-demethyl-12-oxo-calanolide A (20, EC(50) = 7.4 nM, SI = 1417), which demonstrates a druggable profile with 32.7% oral bioavailability in rat, tolerated oral single dose toxicity in mice, and especially the feature of highly efficient suppression of the wild-type HIV-1 and Y181C mutant HIV-1 at an EC(50) = 7.4 nM and EC(50) = 0.46 nM, respectively.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-HIV Agents / chemical synthesis
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Anti-HIV Agents / chemistry
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Anti-HIV Agents / pharmacology*
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Biological Availability
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Brain / drug effects
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Cell Line
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Cell Survival / drug effects
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HIV Infections / drug therapy*
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HIV Infections / genetics
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HIV-1 / drug effects*
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HIV-1 / genetics*
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Inhibitory Concentration 50
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Mice
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Models, Molecular
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Molecular Structure
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Mutation / genetics
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Pyranocoumarins / chemical synthesis
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Pyranocoumarins / chemistry
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Pyranocoumarins / pharmacology*
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Rats
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Structure-Activity Relationship
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Virus Replication / drug effects*
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Virus Replication / genetics
Substances
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10-chloromethyl-11-demethyl-12-oxocalanolide A
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Anti-HIV Agents
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Pyranocoumarins