{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:45:44Z","timestamp":1789577144319,"version":"build-2803163510"},"reference-count":55,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T00:00:00Z","timestamp":1689292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Russian Foundation of Science","award":["22-74-10023"],"award-info":[{"award-number":["22-74-10023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Membranes"],"abstract":"<jats:p>The macrolide polyene antibiotic amphotericin B (AmB), remains a valuable drug to treat systemic mycoses due to its wide antifungal activity and low probability of developing resistance. The high toxicity of AmB, expressed in nephropathy and hemolysis, could be partially resolved by lowering therapeutic AmB concentration while maintaining efficacy. This work discusses the possibility of using plant polyphenols and alkaloids to enhance the pore-forming and consequently antifungal activity of AmB. We demonstrated that phloretin, phlorizin, naringenin, taxifolin, quercetin, biochanin A, genistein, resveratrol, and quinine led to an increase in the integral AmB-induced transmembrane current in the bilayers composed of palmitoyloleoylphosphocholine and ergosterol, while catechin, colchicine, and dihydrocapsaicin did not practically change the AmB activity. Cardamonin, 4\u2032-hydroxychalcone, licochalcone A, butein, curcumin, and piperine inhibited AmB-induced transmembrane current. Absorbance spectroscopy revealed no changes in AmB membrane concentration with phloretin addition. A possible explanation of the potentiation is related to the phytochemical-produced changes in the elastic membrane properties and the decrease in the energy of formation of the lipid mouth of AmB pores, which is partially confirmed by differential scanning microcalorimetry. The possibility of AmB interaction with cholesterol in the mammalian cell membranes instead of ergosterol in fungal membranes, determines its high toxicity. The replacement of ergosterol with cholesterol in the membrane lipid composition led to a complete loss or a significant decrease in the potentiating effects of tested phytochemicals, indicating low potential toxicity of these compounds and high therapeutic potential of their combinations with the antibiotic. The discovered combinations of AmB with plant molecules that enhance its pore-forming ability in ergosterol-enriched membranes, seem to be promising for further drug development in terms of the toxicity decrease and efficacy improvement.<\/jats:p>","DOI":"10.3390\/membranes13070670","type":"journal-article","created":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T01:06:36Z","timestamp":1689555996000},"page":"670","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Triggering the Amphotericin B Pore-Forming Activity by Phytochemicals"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2429-2007","authenticated-orcid":false,"given":"Svetlana S.","family":"Efimova","sequence":"first","affiliation":[{"name":"Laboratory of Membrane and Ion Channel Modeling, Institute of Cytology of Russian Academy of Sciences, Tikhoretsky 4, 194064 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna I.","family":"Malykhina","sequence":"additional","affiliation":[{"name":"Laboratory of Membrane and Ion Channel Modeling, Institute of Cytology of Russian Academy of Sciences, Tikhoretsky 4, 194064 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga S.","family":"Ostroumova","sequence":"additional","affiliation":[{"name":"Laboratory of Membrane and Ion Channel Modeling, Institute of Cytology of Russian Academy of Sciences, Tikhoretsky 4, 194064 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.mycmed.2016.11.001","article-title":"An estimation of burden of serious fungal infections in France","volume":"26","author":"Gangneux","year":"2016","journal-title":"J. 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