Novel N-Substituted oseltamivir derivatives as potent influenza neuraminidase inhibitors: Design, synthesis, biological evaluation, ADME prediction and molecular docking studies.
- Publisher:
- ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
- Publication Type:
- Journal Article
- Citation:
- European journal of medicinal chemistry, 2019, 182, pp. 111635
- Issue Date:
- 2019-11
Closed Access
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1-s2.0-S022352341930769X-main.pdf | Published version | 1.13 MB | Adobe PDF |
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Ye, J | |
dc.contributor.author | Yang, X | |
dc.contributor.author |
Xu, M |
|
dc.contributor.author | Chan, PK-S | |
dc.contributor.author | Ma, C | |
dc.date.accessioned | 2020-05-04T07:55:53Z | |
dc.date.available | 2019-08-19 | |
dc.date.available | 2020-05-04T07:55:53Z | |
dc.date.issued | 2019-11 | |
dc.identifier.citation | European journal of medicinal chemistry, 2019, 182, pp. 111635 | |
dc.identifier.issn | 0223-5234 | |
dc.identifier.issn | 1768-3254 | |
dc.identifier.uri | http://hdl.handle.net/10453/140470 | |
dc.description.abstract | The discovery of novel potent neuraminidase (NA) inhibitors remains an attractive approach for treating infectious diseases caused by influenza. In this study, we describe the design and synthesis of novel N-substituted oseltamivir derivatives for probing the 150-cavity which is nascent to the activity site of NA. NA inhibitory studies showed that new derivatives demonstrated the inhibitory activity with IC50 values at nM level against NA of a clinical influenza virus strain. Moreover, the in silico ADME predictions showed that the selected compounds had comparable properties with oseltamivir carboxylate, which demonstrated the druggablity of these derivatives. Furthermore, molecular docking studies showed that the most potent compound 6f and 10i could adopt different modes of binding interaction with NA, which may provide novel solutions for treating oseltamivir-resistant influenza. Based on the research results, we consider that compounds 6f and 10i have the potential for further studies as novel antiviral agents. | |
dc.format | Print-Electronic | |
dc.language | eng | |
dc.publisher | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER | |
dc.relation.ispartof | European journal of medicinal chemistry | |
dc.relation.isbasedon | 10.1016/j.ejmech.2019.111635 | |
dc.rights | info:eu-repo/semantics/closedAccess | |
dc.subject | 0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, 1115 Pharmacology and Pharmaceutical Sciences | |
dc.subject.classification | Medicinal & Biomolecular Chemistry | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Orthomyxoviridae | |
dc.subject.mesh | Neuraminidase | |
dc.subject.mesh | Enzyme Inhibitors | |
dc.subject.mesh | Antiviral Agents | |
dc.subject.mesh | Microbial Sensitivity Tests | |
dc.subject.mesh | Molecular Structure | |
dc.subject.mesh | Structure-Activity Relationship | |
dc.subject.mesh | Dose-Response Relationship, Drug | |
dc.subject.mesh | Drug Design | |
dc.subject.mesh | Computer Simulation | |
dc.subject.mesh | Oseltamivir | |
dc.subject.mesh | Molecular Docking Simulation | |
dc.subject.mesh | Antiviral Agents | |
dc.subject.mesh | Computer Simulation | |
dc.subject.mesh | Dose-Response Relationship, Drug | |
dc.subject.mesh | Drug Design | |
dc.subject.mesh | Enzyme Inhibitors | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Microbial Sensitivity Tests | |
dc.subject.mesh | Molecular Docking Simulation | |
dc.subject.mesh | Molecular Structure | |
dc.subject.mesh | Neuraminidase | |
dc.subject.mesh | Orthomyxoviridae | |
dc.subject.mesh | Oseltamivir | |
dc.subject.mesh | Structure-Activity Relationship | |
dc.title | Novel N-Substituted oseltamivir derivatives as potent influenza neuraminidase inhibitors: Design, synthesis, biological evaluation, ADME prediction and molecular docking studies. | |
dc.type | Journal Article | |
utslib.citation.volume | 182 | |
utslib.location.activity | France | |
utslib.for | 0304 Medicinal and Biomolecular Chemistry | |
utslib.for | 0305 Organic Chemistry | |
utslib.for | 1115 Pharmacology and Pharmaceutical Sciences | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Engineering and Information Technology | |
pubs.organisational-group | /University of Technology Sydney/Strength - INEXT - Innovation in IT Services and Applications | |
pubs.organisational-group | /University of Technology Sydney/Strength - GBDTC - Global Big Data Technologies | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Engineering and Information Technology/School of Electrical and Data Engineering | |
pubs.organisational-group | /University of Technology Sydney | |
utslib.copyright.status | closed_access | * |
dc.date.updated | 2020-05-04T07:55:52Z | |
pubs.publication-status | Published | |
pubs.volume | 182 | |
utslib.start-page | 111635 |
Abstract:
The discovery of novel potent neuraminidase (NA) inhibitors remains an attractive approach for treating infectious diseases caused by influenza. In this study, we describe the design and synthesis of novel N-substituted oseltamivir derivatives for probing the 150-cavity which is nascent to the activity site of NA. NA inhibitory studies showed that new derivatives demonstrated the inhibitory activity with IC50 values at nM level against NA of a clinical influenza virus strain. Moreover, the in silico ADME predictions showed that the selected compounds had comparable properties with oseltamivir carboxylate, which demonstrated the druggablity of these derivatives. Furthermore, molecular docking studies showed that the most potent compound 6f and 10i could adopt different modes of binding interaction with NA, which may provide novel solutions for treating oseltamivir-resistant influenza. Based on the research results, we consider that compounds 6f and 10i have the potential for further studies as novel antiviral agents.
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