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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Development of a novel family of antifungal agents based on a quinone methide oxime framework
Monika Janeczko1, Maciej Masłyk1, Oleg M Demchuk2
1Department of Molecular Biology, The John Paul II Catholic University of Lublin, ul. Konstantynów 1i, Lublin, 20-708, Poland.
Abstract:
Given the widespread occurrence of fungal infections, the phenomenon of fungal drug resistance, and the limited number of systemic antimycotic therapies, novel chemicals should be developed to control pathogenic fungi. We propose using quinone methide oximes as a novel framework for developing a novel class of antifungal agents. Compound 2 was destroyed mature biofilms at the concentration of 0.5 µg/mL (MIC/4) and prevented hyphal growth of Candida albicans at 0.125 µg/mL (MIC/16). The chemical applied at the concentration of 16-128 µg/mL inhibited the growth of the majority of the clinical isolates of Candida used, including those exhibiting resistance towards systemic drugs. Our safety studies performed with the use of normal human cells revealed that compound 2 was not toxic at the antifungal concentrations tested. Surprisingly, compound 2 showed low inhibitory activity against a set of protein kinases in comparison with its parental compound 1.
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