Janeczko Monika, Masłyk Maciej, Demchuk Oleg M, Kurowska-Okoń Antonina, Kwaśnik Mateusz, Górka Kamila, Martyna Aleksandra, Foll-Josselin Béatrice, Ruchaud Sandrine, Bach Stéphane, Woliński Przemysław, Jasiński Radomir, Mirosław Barbara, Sadczuk Małgorzata, Kubiński Konrad
Department of Molecular Biology, The John Paul II Catholic University of Lublin, ul. Konstantynów 1i, Lublin, 20-708, Poland.
Department of Chemistry, The John Paul II Catholic University of Lublin, ul. Konstantynów 1i, Lublin, 20-708, Poland.
Sci Rep. 2025 Apr 18;15(1):13458. doi: 10.1038/s41598-025-98609-5.
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.
鉴于真菌感染的广泛发生、真菌耐药现象以及全身性抗真菌治疗方法的有限性,应开发新型化学物质来控制致病真菌。我们建议使用醌甲基肟作为开发新型抗真菌剂的新框架。化合物2在浓度为0.5 µg/mL(MIC/4)时可破坏成熟生物膜,并在0.125 µg/mL(MIC/16)时阻止白色念珠菌的菌丝生长。以16 - 128 µg/mL的浓度应用该化学物质可抑制所使用的大多数念珠菌临床分离株的生长,包括那些对全身性药物具有抗性的分离株。我们使用正常人细胞进行的安全性研究表明,化合物2在所测试的抗真菌浓度下无毒。令人惊讶的是,与母体化合物1相比,化合物2对一组蛋白激酶的抑制活性较低。