title: An approach towards the synthesis of potential metal-chelating TSAO-T derivatives as bidentate inhibitors of human immunodeficiency virus type 1 reverse transcriptase.
abstract: 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.
authors.affiliation: Instituto de Química Médica (CSIC), Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Chamorro
authors.forename: M J
authors.initials: MJ
authors.lastname: Camarasa
authors.forename: M J
authors.initials: MJ
authors.lastname: Pérez-Pérez
authors.forename: E
authors.initials: E
authors.lastname: de Clercq
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
authors.forename: A
authors.initials: A
authors.lastname: San Félix
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis*; D000998:Antiviral Agents / Q000138:chemical synthesis; D002460:Cell Line; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology*; D015498:HIV-2 / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013141:Spiro Compounds / Q000494:pharmacology*; D013936:Thymidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014529:Uridine / Q000031:analogs & derivatives; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D000998:Antiviral Agents; D002614:Chelating Agents; D009705:Nucleosides; D018894:Reverse Transcriptase Inhibitors; D013141:Spiro Compounds; D013936:Thymidine; C075132:TSAO-T; D014529:Uridine