BMS Derivatives C7-Linked to β-Cyclodextrin and Hyperbranched Polyglycerol Retain Activity against R5-HIV-1NLAD8 Isolates and Can Be Deemed Potential Microbicides |
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Authors: | Dr Elena Petit Dr Lluís Bosch Prof Anna M Costa Ignacio Rodríguez-Izquierdo Dr Daniel Sepúlveda-Crespo Prof M Angeles Muñoz-Fernández Prof Jaume Vilarrasa |
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Affiliation: | 1. Organic Chemistry Section, Facultat de Química, Universitat de Barcelona, Diagonal 645, 08028 Barcelona, Catalonia, Spain;2. Laboratorio de Inmunobiología Molecular, Hospital General Universitario Gregorio Marañón (HGUGM), Dr. Esquerdo 46, 28007 Madrid, Spain |
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Abstract: | Amides from indole-3-glyoxylic acid and 4-benzoyl-2-methylpiperazine, which are related to entry inhibitors developed by Bristol-Myers Squibb (BMS), have been synthesized with aliphatic chains located at the C7 position of the indole ring. These spacers contain an azido group suitable for the well-known Cu(I)-catalyzed (3+2)-cycloaddition or an activated triple bond for the nucleophilic addition of thiols under physiological conditions. Reaction with polyols (β-cyclodextrin and hyperbranched polyglycerol) decorated with complementary click partners has afforded polyol-BMS-like conjugates that are not cytotoxic (TZM.bl cells) and retain the activity against R5-HIV-1NLAD8 isolates. Thus, potential vaginal microbicides based on entry inhibitors, which can be called of 4th generation, are reported here for the first time. |
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Keywords: | 4th generation microbicides HIV entry inhibitors BMS-type drugs click chemistry hyperbranched polyglycerol |
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