Abstract
A new class of inhibitors of HIV-1 reverse transcriptase obtained by the systematic structural simplification of epicatechin and epigallocatechin gallates are also shown here to inhibit DNA-strand-transfer, a process critical to the completion of the HIV-1-RT reproduction and to recombination-associated mutation of the virus. Up to 80-fold selectivity for DNA-strand-transfer inhibition over polymerase inhibition was observed for a defined subset of these agents. Such specific DNA-strand-transfer inhibitors may have important therapeutic potential.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Anti-HIV Agents / chemical synthesis*
-
Anti-HIV Agents / pharmacology
-
Catechin / analogs & derivatives*
-
Catechin / chemical synthesis
-
Catechin / pharmacology
-
DNA, Single-Stranded / antagonists & inhibitors*
-
DNA, Single-Stranded / metabolism
-
Gallic Acid / analogs & derivatives
-
Gallic Acid / chemical synthesis
-
Gallic Acid / pharmacology
-
HIV Reverse Transcriptase / antagonists & inhibitors*
-
HIV Reverse Transcriptase / metabolism
-
Humans
-
Ribonuclease H / antagonists & inhibitors*
-
Ribonuclease H / metabolism
-
Structure-Activity Relationship
Substances
-
Anti-HIV Agents
-
DNA, Single-Stranded
-
Gallic Acid
-
Catechin
-
HIV Reverse Transcriptase
-
Ribonuclease H
-
gallocatechol