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

Laurene da Costa Els Scheers Antonio Coluccia 1 Alessia Rosetti Manon Roche 2, 3 Johan Neyts 4 Thierry Terme 3 Roberto Cirilli 5 Carmen Mirabelli Romano Silvestri 1 Patrice Vanelle 3
1 Department of Medicinal Chemistry and Technologies
2 APHM - Assistance Publique - Hôpitaux de Marseille
3 ICR - Institut de Chimie Radicalaire
4 Laboratory of Virology and Chemotherapy [KU Leuven]
5 Dipartimento del Farmaco
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 mu M and shows a low toxicity in HeLa cells (CC50 \\textgreater 271 mu M). 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. (C) 2017 Elsevier Masson SAS. All rights reserved.
Keywords : 14 infection absolute-configuration Capsid-binder common cold compound dynamics Enantioseparation entry Heterocycles inhibitors Mosher's method replication rv-b14 virus VP1 protein
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https://hal-amu.archives-ouvertes.fr/hal-01774249
Contributor : Marlene Delhaye <>
Submitted on : Monday, April 23, 2018 - 3:00:55 PM
Last modification on : Thursday, October 29, 2020 - 3:08:13 AM

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Laurene da Costa, Els Scheers, Antonio Coluccia, Alessia Rosetti, Manon Roche, et al.. Heterocyclic pharmacochemistry of new rhinovirus antiviral agents: A combined computational and experimental study. European Journal of Medicinal Chemistry, Elsevier, 2017, 140, pp.528--541. ⟨10.1016/j.ejmech.2017.09.036⟩. ⟨hal-01774249⟩

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