An approach towards the synthesis of potential metal-chelating TSAO-T derivatives as bidentate inhibitors of human immunodeficiency virus type 1 reverse transcriptase

Antivir Chem Chemother. 1998 Sep;9(5):413-22.


Novel derivatives of the potent human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitor TSAO-T have been designed, synthesized and tested for their in vitro antiretroviral activity against HIV. These TSAO-T derivatives have been designed as potential bidentate inhibitors of HIV-1 RT, which combine in their structure the functionality of a non-nucleoside RT inhibitor (TSAO-T) and a bivalent ion-chelating moiety (a beta-diketone moiety) linked through an appropriate spacer to the N-3 of thymine of TSAO-T. Some of the new compounds have an anti-HIV-1 activity comparable to that of the parent compound TSAO-T, but display a markedly increased antiviral selectivity. There was a clear relationship between antiviral activity and the length of the spacer group that links the TSAO molecule with the chelating moiety. A shorter spacer invariably resulted in increased antiviral potency. None of the TSAO-T derivatives were endowed with anti-HIV-2 activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis*
  • Antiviral Agents / chemical synthesis
  • Cell Line
  • Chelating Agents / chemical synthesis*
  • Chelating Agents / pharmacology
  • HIV-1 / drug effects
  • HIV-1 / enzymology*
  • HIV-2 / drug effects
  • Humans
  • Molecular Structure
  • Nucleosides / chemical synthesis*
  • Nucleosides / pharmacology
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / pharmacology
  • Spiro Compounds / pharmacology*
  • Thymidine / analogs & derivatives*
  • Thymidine / pharmacology
  • Uridine / analogs & derivatives
  • Virus Replication / drug effects


  • Anti-HIV Agents
  • Antiviral Agents
  • Chelating Agents
  • Nucleosides
  • Reverse Transcriptase Inhibitors
  • Spiro Compounds
  • Thymidine
  • TSAO-T
  • Uridine