Structure-Based Drug Design of Potent Pyrazole Derivatives against Rhinovirus Replication

Journal of Medicinal Chemistry
Laurène Da CostaPatrice Vanelle

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 (EC50 < 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.

References

Mar 10, 1989·Cell·J M GreveA McClelland
Sep 15, 1993·Structure·M A OliveiraM A McKinlay
Mar 1, 1994·Proceedings of the National Academy of Sciences of the United States of America·F HoferD Blaas
Oct 3, 1999·Antimicrobial Agents and Chemotherapy·A K PatickS T Worland
Oct 31, 2000·The Pediatric Infectious Disease Journal·T Chonmaitree, T Heikkinen
Aug 21, 2001·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·A PitkärantaA Vaheri
Dec 4, 2003·Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology·Inesz van BentenWytske Fokkens
Mar 30, 2004·Proteins·Matthew P JacobsonRichard A Friesner
Apr 6, 2004·Nature Structural & Molecular Biology·Nuria VerdaguerDieter Blaas
Aug 9, 2005·The Journal of Allergy and Clinical Immunology·Samuel L Friedlander, William W Busse
Aug 23, 2005·Proceedings of the American Thoracic Society·Jadwiga A Wedzicha
Oct 4, 2006·Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology·F M ChantziD A Kafetzis
Apr 13, 2007·Journal of Virology·Umesh Katpally, Thomas J Smith
Apr 3, 2008·Medicinal Research Reviews·Armando M De PalmaJohan Neyts
Oct 7, 2008·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·Ville PeltolaOlli Ruuskanen
May 29, 2010·Emerging Infectious Diseases·Marina B de AlmeidaLuiz Vicente F da Silva Filho
Oct 5, 2010·American Journal of Respiratory and Critical Care Medicine·Patrick MalliaSebastian L Johnston
Mar 3, 2011·Proceedings of the American Thoracic Society·Birgit Winther
Dec 30, 2011·Journal of Clinical Microbiology·Colleen S KraftG Marshall Lyon
Jan 9, 2013·Clinical Microbiology Reviews·Samantha E JacobsThomas J Walsh
Apr 13, 2013·Journal of Computer-aided Molecular Design·G Madhavi SastryWoody Sherman
Nov 26, 2013·Angewandte Chemie·Julie BroggiPatrice Vanelle
Nov 28, 2013·Scientifica·Marc B Hershenson
Mar 19, 2014·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·Anne GoffardLaurence Delhaes
Apr 12, 2012·ACS Medicinal Chemistry Letters·Susanne C FeilCraig J Morton
Jun 21, 2014·The Journal of Antimicrobial Chemotherapy·Céline LacroixPieter Leyssen
Oct 2, 2014·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·J E Gern
Apr 8, 2015·Proceedings of the National Academy of Sciences of the United States of America·Yury A BochkovJames E Gern
Aug 12, 2015·ChemMedChem·Vadim A MakarovMichaela Schmidtke
Jan 14, 2016·Viruses·Léna Royston, Caroline Tapparel
Apr 7, 2016·European Journal of Medicinal Chemistry·Laurène Da CostaPatrice Vanelle
Oct 26, 2016·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·Elina SeppäläHeikki Hyöty
Jan 20, 2017·Journal of Virology·Ann C Palmenberg
Jun 6, 2017·Journal of Medicinal Chemistry·Jinwoo KimYoung-Sik Jung
Oct 11, 2017·European Journal of Medicinal Chemistry·Laurène Da CostaPatrice Vanelle
Oct 19, 2017·Journal of Natural Products·Benedetta FoisFilippo Cottiglia

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Acute viral rhinopharyngitis

Acute viral rhinopharyngitis, also known as "common cold", is an acute, self-limiting viral infection of the upper respiratory tract involving the nose, sinuses, pharynx and larynx. Discover the latest research on acute viral rhinopharyngitis here.