The Anti-Candida albicans Agent 4-AN Inhibits Multiple Protein Kinases
Maciej Masłyk,
Monika Janeczko,
Aleksandra Martyna,
Sławomir Czernik,
Małgorzata Tokarska-Rodak,
Marta Chwedczuk,
Béatrice Foll-Josselin,
Sandrine Ruchaud,
Stéphane Bach,
Oleg M. Demchuk,
Konrad Kubiński
Affiliations
Maciej Masłyk
Department of Molecular Biology, Institute of Biotechnology, The John Paul II Catholic University of Lublin, ul. Konstantynów 1i, 20-708 Lublin, Poland
Monika Janeczko
Department of Molecular Biology, Institute of Biotechnology, The John Paul II Catholic University of Lublin, ul. Konstantynów 1i, 20-708 Lublin, Poland
Aleksandra Martyna
Department of Molecular Biology, Institute of Biotechnology, The John Paul II Catholic University of Lublin, ul. Konstantynów 1i, 20-708 Lublin, Poland
Sławomir Czernik
Innovation Research Centre, Pope John Paul II State School of Higher Education in Biala Podlaska, Sidorska 95/97, 21-500 Biala Podlaska, Poland
Małgorzata Tokarska-Rodak
Institute of Health Sciences, Pope John Paul II State School of Higher Education in Biala Podlaska, Sidorska 95/97, 21-500 Biala Podlaska, Poland
Marta Chwedczuk
Innovation Research Centre, Pope John Paul II State School of Higher Education in Biala Podlaska, Sidorska 95/97, 21-500 Biala Podlaska, Poland
Béatrice Foll-Josselin
Sorbonne Université, USR3151 CNRS/UPMC, Plateforme de criblage KISSf (Kinase Inhibitor Specialized Screening Facility), Station Biologique, Place Georges Teissier, F-29688 Roscoff, France
Sandrine Ruchaud
Sorbonne Université, USR3151 CNRS/UPMC, Plateforme de criblage KISSf (Kinase Inhibitor Specialized Screening Facility), Station Biologique, Place Georges Teissier, F-29688 Roscoff, France
Stéphane Bach
Sorbonne Université, USR3151 CNRS/UPMC, Plateforme de criblage KISSf (Kinase Inhibitor Specialized Screening Facility), Station Biologique, Place Georges Teissier, F-29688 Roscoff, France
Oleg M. Demchuk
Pharmaceutical Research Institute, Rydygiera Street 8, 01-793 Warsaw, Poland
Konrad Kubiński
Department of Molecular Biology, Institute of Biotechnology, The John Paul II Catholic University of Lublin, ul. Konstantynów 1i, 20-708 Lublin, Poland
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.
