Camphor-based CCR5 blocker lead compounds – a computational and experimental approach
| Autor: | Gonçalo C. Justino, Pedro F. Pinheiro, M. Fernanda N. N. Carvalho, João Gonçalves, Alexandra P. S. Roseiro, Marta C. Justino, Ana S. O. Knittel |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Chemistry Stereochemistry General Chemical Engineering General Chemistry CCR5 receptor antagonist Transmembrane protein 3. Good health 03 medical and health sciences Chemokine receptor chemistry.chemical_compound Camphor 030104 developmental biology Viral entry Hydroxymethyl Receptor Maraviroc |
| Zdroj: | RSC Advances |
| ISSN: | 2046-2069 |
| DOI: | 10.1039/c6ra09627a |
| Popis: | The C–C chemokine receptor type 5 (CCR5) is a transmembrane receptor that plays a pivotal role as a HIV anchor to human cell membranes, mediating viral entry. CCR5 antagonists, acting by blocking the receptor and preventing its interaction with the HIV proteins, are key agents towards effective anti-viral therapy. This work describes the computational study, synthesis and viral inhibition assay of a number of camphor derivatives as a first step towards new drug leads to block this specific entry pathway. Viral inhibition assays have identified three molecules, camphor carboxylic acid, its tri(hydroxymethyl)aminomethane amide derivative, and an hydroxyl-imide camphor derivative as promising agents to develop new drugs, with IC50 values (0.16, 0.22 and 1.02 μM, respectively) one order below that of maraviroc (0.02 μM), a clinically used CCR5 antagonist. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|