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The Anti-Candida albicans Agent 4-AN Inhibits Multiple Protein Kinases

Authors :
Oleg M. Demchuk
Aleksandra Martyna
Béatrice Foll-Josselin
Sławomir Czernik
Małgorzata Tokarska-Rodak
Sandrine Ruchaud
Monika Janeczko
Marta Chwedczuk
Maciej Masłyk
Konrad Kubiński
Stéphane Bach
Laboratoire de Biologie Intégrative des Modèles Marins (LBI2M)
Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR)
Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
John Paul II Catholic University of Lublin (KUL)
Pope John Paul II State School of Higher Education in Biała Podlaska
Phophorylation de protéines et Pathologies Humaines (P3H)
Station biologique de Roscoff [Roscoff] (SBR)
Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Pharmaceutical Research Institute
Source :
Molecules, Molecules, MDPI, 2019, 24 (1), pp.153. ⟨10.3390/molecules24010153⟩, Molecules, Vol 24, Iss 1, p 153 (2019), Volume 24, Issue 1
Publication Year :
2019
Publisher :
HAL CCSD, 2019.

Abstract

International audience; Small molecules containing quinone and/or oxime moieties have been found as promising anti-fungal agents. One of them is 4-AN, a recently reported potent anti-Candida compound, which inhibits the formation of hyphae, decreases the level of cellular phosphoproteome, and finally shows no toxicity towards human erythrocytes and zebrafish embryos. Here, further research on 4-AN is presented. The results revealed that the compound: (i) Kills Candida clinical isolates, including these with developed antibiotic resistance, (ii) affects mature biofilm, and (iii) moderately disrupts membrane permeability. Atomic force microscopy studies revealed a slight influence of 4-AN on the cell surface architecture. 4-AN was also shown to inhibit multiple various protein kinases, a characteristic shared by most of the ATP-competitive inhibitors. The presented compound can be used in novel strategies in the fight against candidiasis, and reversible protein phosphorylation should be taken into consideration as a target in designing these strategies.

Details

Language :
English
ISSN :
14203049
Database :
OpenAIRE
Journal :
Molecules, Molecules, MDPI, 2019, 24 (1), pp.153. ⟨10.3390/molecules24010153⟩, Molecules, Vol 24, Iss 1, p 153 (2019), Volume 24, Issue 1
Accession number :
edsair.doi.dedup.....e8ba6a679dc560fe4e507183c2d4badf
Full Text :
https://doi.org/10.3390/molecules24010153⟩