Abstract
The viral enzyme integrase is essential for the replication of human immunodeficiency virus type 1 (HIV-1) and represents a remaining target for antiretroviral drugs. Here, we describe the modification of a quinolone antibiotic to produce the novel integrase inhibitor JTK-303 (GS 9137) that blocks strand transfer by the viral enzyme. It shares the core structure of quinolone antibiotics, exhibits an IC50 of 7.2 nM in the strand transfer assay, and shows an EC50 of 0.9 nM in an acute HIV-1 infection assay.
MeSH terms
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Anti-Bacterial Agents / chemical synthesis*
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / pharmacology
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Cell Line
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DNA, Viral / chemistry
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HIV Integrase / metabolism*
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HIV Integrase Inhibitors / chemical synthesis*
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HIV Integrase Inhibitors / chemistry
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HIV Integrase Inhibitors / pharmacology
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HIV-1 / drug effects
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HIV-1 / enzymology
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Humans
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Quinolones / chemical synthesis*
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Quinolones / chemistry
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Quinolones / pharmacology
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Structure-Activity Relationship
Substances
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Anti-Bacterial Agents
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DNA, Viral
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HIV Integrase Inhibitors
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Quinolones
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elvitegravir
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HIV Integrase