The Anti- Agent 4-AN Inhibits Multiple Protein Kinases.

The Anti- Agent 4-AN Inhibits Multiple Protein Kinases.

Masłyk, Maciej;Janeczko, Monika;Martyna, Aleksandra;Czernik, Sławomir;Tokarska-Rodak, Małgorzata;Chwedczuk, Marta;Foll-Josselin, Béatrice;Ruchaud, Sandrine;Bach, Stéphane;Demchuk, Oleg M;Kubiński, Konrad;
Molecules (Basel, Switzerland) 2019 Vol. 24
223
masyk2019themolecules

Abstract

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- 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 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.

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