title: Synthesis and in vitro activity of novel N-3 acylated TSAO-T compounds against HIV-1 and HCV.
abstract: Preparation of a small library of derivatives of the potent HIV-1 Reverse Transcriptase inhibitor TSAO-T bearing mono or di-carbonyl substituents (designed after docking analysis) at position N-3 is reported. A one-pot synthetic methodology has been developed that involves: (i) mono-reaction of TSAO-T with glutaryl dichloride under phase transfer conditions and (ii) in situ acyclic substitution of the remaining chloro atom by oxygen or nitrogen nucleophiles. The method is compatible with the polyfunctionality of the TSAO-T molecule, proceeds with high conversion yields and allows introducing molecular diversity. The anti-HIV-1 and -HCV activity was studied in cell culture. The new N-3 acylated TSAO-T derivatives are active against HIV-1 (nanomolar range). Anti-HCV activity was observed in the micromolar range, that is at compound concentrations that were found cytostatic against human T-lymphocytes.
authors: Laboratoire des Glucides (UMR 6219), Université de Picardie Jules Verne, 33 rue Saint Leu, 80039 Amiens, France.
authors: Marina
authors: M
authors: Moura
authors: Solen
authors: S
authors: Josse
authors: Albert
authors: A
authors: Nguyen Van Nhien
authors: Carole
authors: C
authors: Fournier
authors: Gilles
authors: G
authors: Duverlie
authors: Sandrine
authors: S
authors: Castelain
authors: Elena
authors: E
authors: Soriano
authors: José
authors: J
authors: Marco-Contelles
authors: Jan
authors: J
authors: Balzarini
authors: Denis
authors: D
authors: Postel
mesh_terms: D002460:Cell Line; D060326:Chemistry Techniques, Synthetic; D015658:HIV Infections / Q000188:drug therapy / Q000201:enzymology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D016174:Hepacivirus / Q000187:drug effects*; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D008958:Models, Molecular; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014529:Uridine / Q000031:analogs & derivatives
chemical_list: D018894:Reverse Transcriptase Inhibitors; D054852:Small Molecule Libraries; D013141:Spiro Compounds; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D013936:Thymidine; C075132:TSAO-T; D014529:Uridine