Flexible docking of pyridinone derivatives into the non-nucleoside inhibitor binding site of HIV-1 reverse transcriptase

Bioorg Med Chem. 2004 Dec 1;12(23):6085-95. doi: 10.1016/j.bmc.2004.09.008.

Abstract

Potent non-nucleoside reverse transcriptase inhibitors (NNRTIs) of the pyridinone derivative type were docked into nine NNRTIs binding pockets of HIV-1 reverse transcriptase (RT) structures. The docking results indicate that pyridinone analogues adopt a butterfly conformation and share the same binding mode as the crystal inhibitors in the pocket geometries of nevirapine, 1051U91, 9-Cl-TIBO, Cl-alpha-APA, efavirenz, UC-781, and S-1153. The results are in agreement with the data concerning mutational and structure-activity relationships available for pyridinone analogues and aid in the understanding, at the molecular level, of the biological response of published hybrid pyridinone molecules. Strategies to design further pyridinone derivatives active against RT containing mutations are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemistry
  • Binding Sites
  • Computer Simulation*
  • HIV Reverse Transcriptase / chemistry*
  • Models, Molecular
  • Pyridones / chemistry*
  • Reverse Transcriptase Inhibitors / chemistry*
  • Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • Pyridones
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase