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Authors = Dorothée Bardiot

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26 pages, 1214 KiB  
Article
Synthesis, Structure–Activity Relationships, and Antiviral Profiling of 1-Heteroaryl-2-Alkoxyphenyl Analogs as Inhibitors of SARS-CoV-2 Replication
by Dorothée Bardiot, Laura Vangeel, Mohamed Koukni, Philippe Arzel, Marleen Zwaagstra, Heyrhyoung Lyoo, Patrick Wanningen, Shamshad Ahmad, Linlin Zhang, Xinyuanyuan Sun, Adrien Delpal, Cecilia Eydoux, Jean-Claude Guillemot, Eveline Lescrinier, Hugo Klaassen, Pieter Leyssen, Dirk Jochmans, Karolien Castermans, Rolf Hilgenfeld, Colin Robinson, Etienne Decroly, Bruno Canard, Eric J. Snijder, Martijn J. van Hemert, Frank van Kuppeveld, Patrick Chaltin, Johan Neyts, Steven De Jonghe and Arnaud Marchandadd Show full author list remove Hide full author list
Molecules 2022, 27(3), 1052; https://doi.org/10.3390/molecules27031052 - 4 Feb 2022
Cited by 5 | Viewed by 4997
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has led to a pandemic, that continues to be a huge public health burden. Despite the availability of vaccines, there is still a need for small-molecule antiviral drugs. In an [...] Read more.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has led to a pandemic, that continues to be a huge public health burden. Despite the availability of vaccines, there is still a need for small-molecule antiviral drugs. In an effort to identify novel and drug-like hit matter that can be used for subsequent hit-to-lead optimization campaigns, we conducted a high-throughput screening of a 160 K compound library against SARS-CoV-2, yielding a 1-heteroaryl-2-alkoxyphenyl analog as a promising hit. Antiviral profiling revealed this compound was active against various beta-coronaviruses and preliminary mode-of-action experiments demonstrated that it interfered with viral entry. A systematic structure–activity relationship (SAR) study demonstrated that a 3- or 4-pyridyl moiety on the oxadiazole moiety is optimal, whereas the oxadiazole can be replaced by various other heteroaromatic cycles. In addition, the alkoxy group tolerates some structural diversity. Full article
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9 pages, 192 KiB  
Article
Identification of Fungicidal 2,6-Disubstituted Quinolines with Activity against Candida Biofilms
by Nicolas Delattin, Dorothée Bardiot, Arnaud Marchand, Patrick Chaltin, Katrijn De Brucker, Bruno P. A. Cammue and Karin Thevissen
Molecules 2012, 17(10), 12243-12251; https://doi.org/10.3390/molecules171012243 - 18 Oct 2012
Cited by 10 | Viewed by 7076
Abstract
We have identified two subseries of 2,6-disubstituted quinolines, consisting of 6-amide and 6-urea derivatives, which are characterized by fungicidal activity against Candida albicans with minimal fungicidal concentration (MFC) values C. albicans, in particular compounds 1, 5 and 6 characterized by MFC values [...] Read more.
We have identified two subseries of 2,6-disubstituted quinolines, consisting of 6-amide and 6-urea derivatives, which are characterized by fungicidal activity against Candida albicans with minimal fungicidal concentration (MFC) values < 15 µM. The 6-amide derivatives displayed the highest fungicidal activity against C. albicans, in particular compounds 1, 5 and 6 characterized by MFC values of 6.25–12.5 µM. Compounds 1 and 5 of this series displayed fungicidal activity against the emerging pathogen Candida glabrata (MFC < 50 µM). The 6-amide derivatives 1, 2, 5, and 6 and the 6-urea derivatives 10, 12, 13 and 15 could also eradicate C. albicans biofilms. We found that the 6-urea derivatives 10, 13, and 15 induced accumulation of endogenous reactive oxygen species in Candida albicans biofilms. Full article
(This article belongs to the Special Issue Advances in Medicinal Chemistry of Antibiotics)
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