BMS Derivatives C7-Linked to β-Cyclodextrin and Hyperbranched Polyglycerol Retain Activity against R5-HIV-1NLAD8 Isolates and Can Be Deemed Potential Microbicides
| Autor: | Daniel Sepúlveda-Crespo, Ignacio Rodriguez-Izquierdo, Anna M. Costa, Jaume Vilarrasa, M. Ángeles Muñoz-Fernández, Elena Petit, Lluís Bosch |
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| Rok vydání: | 2021 |
| Předmět: |
Sida
01 natural sciences Biochemistry Drug Discovery Ciclodextrines General Pharmacology Toxicology and Pharmaceutics Pharmacology Indole test chemistry.chemical_classification Cyclodextrins Nucleophilic addition Cyclodextrin 010405 organic chemistry Chemistry Vaginal microbicide Organic Chemistry Triple bond Combinatorial chemistry Amides 0104 chemical sciences Microbicides for sexually transmitted diseases 010404 medicinal & biomolecular chemistry Click chemistry Molecular Medicine AIDS (Disease) Conjugate |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona |
| Popis: | Amides from indole-3-glyoxylic acid and 4 - benzoyl-2-methyl-piperazine, 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 less known 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-1 NLAD8 isolates. Thus, potential vaginal microbicides based on entry inhibitors, which can be called of 4th generation, are reported here for the first time. |
| Databáze: | OpenAIRE |
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