title: Thiated derivatives of 2',3'-dideoxy-3'-fluorothymidine: synthesis, in vitro anti-HIV-1 activity and interaction with recombinant drug resistant HIV-1 reverse transcriptase forms.
abstract: Various thiated analogues of thymine 2',3'-dideoxy-3'-fluoronucleoside (FLT) and their 5'-monophosphates and 5'-triphosphates were prepared with the use of modified multistep procedures. The thiated analogues of FLT and FLTMP were evaluated against the wild type and drug- and multidrug-resistant strains of HIV-1, using the replicative phenotyping format of the deCIPhR assay, and showed potent inhibition of drug-resistant HIV-1 strains at low cytotoxicity. Additionally, inhibition of recombinant drug resistant forms of reverse transcriptase from single and multiple HIV-1 mutants by the synthesized 5'-triphosphates was investigated. The strongest inhibition was observed for K103N and Δ67 mutants and the most potent anti-HIV-1 activity against drug resistant strains and the lowest cytotoxicity was exerted by S4FLTMP and FLTMP which may be regarded as potential anti-HIV/AIDS agents.
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 5A Pawinskiego St., 02-106 Warszawa, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Miazga
authors.forename: François
authors.initials: F
authors.lastname: Hamy
authors.forename: Séverine
authors.initials: S
authors.lastname: Louvel
authors.forename: Thomas
authors.initials: T
authors.lastname: Klimkait
authors.forename: Zofia
authors.initials: Z
authors.lastname: Pietrusiewicz
authors.forename: Anna
authors.initials: A
authors.lastname: Kurzyńska-Kokorniak
authors.forename: Marek
authors.initials: M
authors.lastname: Figlerowicz
authors.forename: Patrycja
authors.initials: P
authors.lastname: Wińska
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Kulikowski
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D015224:Dideoxynucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000502:physiology; D006801:Humans; D007700:Kinetics; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; C002854:alovudine