Heterocyclic pharmacochemistry of new rhinovirus antiviral agents: A combined computational and experimental study

Laurène Da Costa, Els Scheers, Antonio Coluccia, Alessia Rosetti, Manon Roche, Johan Neyts, Thierry Terme, Roberto Cirilli, Carmen Mirabelli, Romano Silvestri, Patrice Vanelle

Research output: Contribution to journalArticlepeer-review

Abstract

Rhinovirus (RV), member of the Enterovirus genus, is known to be involved in more than half of the common colds. Through advances in molecular biology, rhinoviruses have also been associated with exacerbations of chronic pulmonary diseases (e.g. asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis). In the current investigation, we develop a novel series of 4,5-dimethoxybenzyl derivatives that potently inhibits rhinovirus replication. Compound (S)-7f blocks RV-B14 replication with an EC50 value of 0.25 μM and shows a low toxicity in HeLa cells (CC50 > 271 μM). Enantioseparation followed by an absolute configuration determination by a Mosher's method revealed the interest of enantiopure compounds. Molecular docking studies permitted the identification of key biological interactions within the drug-binding pocket and an in silico drug-like study revealed a good potential for the development of these derivatives.

Original languageEnglish
Pages (from-to)528-541
Number of pages14
JournalEuropean Journal of Medicinal Chemistry
Volume140
DOIs
Publication statusPublished - Nov 10 2017

Keywords

  • Capsid-binder
  • Enantioseparation
  • Heterocycles
  • Mosher's method
  • RV-B14
  • VP1 protein

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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