BMS Derivatives C7-Linked to β-Cyclodextrin and Hyperbranched Polyglycerol Retain Activity against R5-HIV-1NLAD8 Isolates and Can Be Deemed Potential Microbicides.
Elena PetitLluís BoschAnna M CostaIgnacio Rodríguez-IzquierdoDaniel Sepúlveda-CrespoM Angeles Muñoz-FernándezJaume VilarrasaPublished in: ChemMedChem (2021)
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.
Keyphrases
- hiv testing
- antiretroviral therapy
- hiv positive
- hiv infected
- men who have sex with men
- human immunodeficiency virus
- hepatitis c virus
- hiv aids
- induced apoptosis
- human health
- ionic liquid
- genetic diversity
- capillary electrophoresis
- room temperature
- risk assessment
- cell proliferation
- cell death
- mass spectrometry
- climate change
- metal organic framework
- electron transfer