Inhibitors of HIV-1 replication [corrected; erratum to be published] that inhibit HIV integrase.
HIV-1 replication depends on the viral enzyme integrase that mediates integration of a DNA copy of the virus into the host cell genome. This enzyme represents a novel target to which antiviral agents might be directed. Three compounds, 3,5-dicaffeoylquinic acid, 1-methoxyoxalyl-3,5-dicaffeoylquinic acid, and L-chicoric acid, inhibit HIV-1 integrase in biochemical assays at concentrations ranging from 0.06-0.66 microgram/ml; furthermore, these compounds inhibit HIV-1 replication in tissue culture at 1-4 microgram/ml. The toxic concentrations of these compounds are fully 100-fold greater than their antiviral concentrations. These compounds represent a potentially important new class of antiviral agents that may contribute to our understanding of the molecular mechanisms of viral integration. Thus, the dicaffeoylquinic acids are promising leads to new anti-HIV therapeutics and offer a significant advance in the search for new HIV enzyme targets as they are both specific for HIV-1 integrase and active against HIV-1 in tissue culture.
Robinson
W E
WE
Department of Pathology, University of California, Irvine 92717-4800, USA.
Reinecke
M G
MG
Abdel-Malek
S
S
Jia
Q
Q
Chow
S A
SA
D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D002109:Caffeic Acids; D002460:Cell Line; D002726:Chlorogenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004254:DNA Nucleotidyltransferases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000201:enzymology / Q000502:physiology*; D006801:Humans; D019426:Integrases; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D013386:Succinates / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
C100436:1-methoxyoxalyl-3,5-dicaffeoylquinic acid; D000998:Antiviral Agents; D002109:Caffeic Acids; D004791:Enzyme Inhibitors; D009838:Oligodeoxyribonucleotides; D013386:Succinates; D002726:Chlorogenic Acid; D004254:DNA Nucleotidyltransferases; D019426:Integrases; C100434:3,5-dicaffeoylquinic acid; C100435:chicoric acid