Year: 2018
Type: article
Abstract: Rhinoviruses (RVs) have been linked to exacerbations of many pulmonary diseases, thus increasing morbidity and/or mortality in subjects at risk. Unfortunately, the wide variety of RV genotypes constitutes a major hindrance for the development of Rhinovirus replication inhibitors. In the current investigation, we have developed a novel series of pyrazole derivatives that potently inhibit the Rhinovirus replication. Compounds 10e and 10h behave as early stage inhibitors of Rhinovirus infection with a broad-spectrum activity against RV-A and RV-B species (EC 50 < 0.1 μM). We also evaluate the dynamics of the emerging resistance of these promising compounds and their in vitro genotoxicity. Molecular docking experiments shed light on the pharmacophoric elements interacting with residues of the drug-binding pocket.
Source: Journal of Medicinal Chemistry
Institutions: Centre National de la Recherche Scientifique, Aix-Marseille Université, Institut de Chimie Radicalaire, Rega Institute for Medical Research, KU Leuven, Istituto Pasteur, Sapienza University of Rome, Istituto Superiore di Sanità, World Health Organization - Italy, Institut Méditerranéen de Biodiversité et d'Ecologie Marine et Continentale, Institut de Recherche pour le Développement
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W2889138138