A possible improvement for structure-based drug design illustrated by the discovery of a Tat HIV-1 inhibitor

Bioorg Med Chem Lett. 2004 Mar 22;14(6):1543-6. doi: 10.1016/j.bmcl.2003.12.095.

Abstract

The HIV-1 Tat protein is a promising target for AIDS therapy, due to its extra-cellular roles against the immune system. From the 2D-NMR structure of Tat, we have designed molecules, called TDS, able to bind to Tat and inhibit HIV-1 replication in vitro. This new family of antivirals is composed of a triphenylene aromatic ring substituted with at least one carbon chain bearing a succinimide group. These ligands are prepared from triphenylene or 2,6,10-trimethylphenylene in 3-6 steps depending on the target molecule.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemistry*
  • Anti-HIV Agents / metabolism
  • Anti-HIV Agents / pharmacology*
  • Drug Design*
  • Gene Products, tat / antagonists & inhibitors*
  • Gene Products, tat / metabolism
  • HIV-1 / drug effects*
  • HIV-1 / metabolism
  • Humans
  • Structure-Activity Relationship
  • tat Gene Products, Human Immunodeficiency Virus

Substances

  • Anti-HIV Agents
  • Gene Products, tat
  • tat Gene Products, Human Immunodeficiency Virus