Περίληψη:
Fungal infections constitute an emerging threat and a prevalent health problem due to increasing number of immunocompromised people and pharmacological or other treatments aiming at viral infections, cancer or allergies. Currently used antifungals suffer from inefficiency, toxic side effects and developing drug-resistance. Additionally, over the last two decades no new classes of antifungals have been approved, emphasizing the urgent need for developing a novel generation of antifungals. Here, we investigate the antifungal activity of a series of chemically synthesized Hydroxytyrosol (HT) analogs. HT is one of the major phenolic compounds in olive oil, shown to possess radical-scavenging antioxidant, antiproliferative, proapoptotic and anti-inflammatory activities. No previous report has studied HT analogs as antifungals. We show that specific analogs have broad and strong antifungal activity, significantly stronger than the parent compound HT. Using Aspergillus nidulans as an in vivo cellular model system, we show that antifungal HT analogs have an unprecedented efficiency in fungal plasma membrane destruction. Importantly, antifungal HT analogs did not show toxicity in a mammalian cell line, whereas no resistance to HT analogs was obtained by standard mutagenesis. Our results open the way for the development of a novel, efficient and safer class of antifungals. Copyright © 2018 Diallinas, Rafailidou, Kalpaktsi, Komianou, Tsouvali, Zantza, Mikros, Skaltsounis and Kostakis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Συγγραφείς:
Diallinas, G.
Rafailidou, N.
Kalpaktsi, I.
Komianou, A.C.
Tsouvali, V.
Zantza, I.
Mikros, E.
Skaltsounis, A.L.
Kostakis, I.K.
Λέξεις-κλειδιά:
antifungal agent; hydroxytyrosol; olive oil, animal cell; antibacterial activity; antibiotic resistance; antibiotic sensitivity; antifungal activity; antiinflammatory activity; antioxidant activity; antiproliferative activity; Article; Aspergillus nidulans; Bacillus subtilis; bacterial growth; bacterial infection; cell destruction; controlled study; cytotoxicity assay; epifluorescence microscopy; Escherichia coli; free radical scavenging assay; fungus growth; immunocompromised patient; Klebsiella; mouse; MTT assay; mutagenesis; mycosis; Neuro-2a cell line; nonhuman; Pseudomonas aeruginosa; Pseudomonas fluorescens; Staphylococcus aureus
