{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:55:59Z","timestamp":1790009759579,"version":"4.0.1"},"reference-count":64,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T00:00:00Z","timestamp":1673395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["21-74-20102"],"award-info":[{"award-number":["21-74-20102"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["21-74-10115"],"award-info":[{"award-number":["21-74-10115"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Arab Republic of Egypt","award":["21-74-20102"],"award-info":[{"award-number":["21-74-20102"]}]},{"name":"Arab Republic of Egypt","award":["21-74-10115"],"award-info":[{"award-number":["21-74-10115"]}]},{"name":"Russian Federation","award":["21-74-20102"],"award-info":[{"award-number":["21-74-20102"]}]},{"name":"Russian Federation","award":["21-74-10115"],"award-info":[{"award-number":["21-74-10115"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Polyene antifungal amphotericin B (AmB) has been used for over 60 years, and remains a valuable clinical treatment for systemic mycoses, due to its broad antifungal activity and low rate of emerging resistance. There is no consensus on how exactly it kills fungal cells but it is certain that AmB and the closely-related nystatin (Nys) can form pores in membranes and have a higher affinity towards ergosterol than cholesterol. Notably, the high nephro- and hemolytic toxicity of polyenes and their low solubility in water have led to efforts to improve their properties. We present the synthesis of new amphotericin and nystatin amides and a comparative study of the effects of identical modifications of AmB and Nys on the relationship between their structure and properties. Generally, increases in the activity\/toxicity ratio were in good agreement with increasing ratios of selective permeabilization of ergosterol- vs. cholesterol-containing membranes. We also show that the introduced modifications had an effect on the sensitivity of mutant yeast strains with alterations in ergosterol biosynthesis to the studied polyenes, suggesting a varying affinity towards intermediate ergosterol precursors. Three new water-soluble nystatin derivatives showed a prominent improvement in safety and were selected as promising candidates for drug development.<\/jats:p>","DOI":"10.3390\/antibiotics12010151","type":"journal-article","created":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T01:32:26Z","timestamp":1673487146000},"page":"151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Semisynthetic Amides of Amphotericin B and Nystatin A1: A Comparative Study of In Vitro Activity\/Toxicity Ratio in Relation to Selectivity to Ergosterol Membranes"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1091-1011","authenticated-orcid":false,"given":"Anna","family":"Tevyashova","sequence":"first","affiliation":[{"name":"Gause Institute of New Antibiotics, 11 B. Pirogovskaya, 119021 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2429-2007","authenticated-orcid":false,"given":"Svetlana","family":"Efimova","sequence":"additional","affiliation":[{"name":"Institute of Cytology of the Russian Academy of Sciences, 4 Tikhoretsky, 194064 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7250-4740","authenticated-orcid":false,"given":"Alexander","family":"Alexandrov","sequence":"additional","affiliation":[{"name":"Federal Research Center \u201cFundamentals of Biotechnology\u201d of the Russian Academy of Sciences, Bach Institute of Biochemistry, 33 Leninsky Ave., bld. 2, 119071 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Omelchuk","sequence":"additional","affiliation":[{"name":"Gause Institute of New Antibiotics, 11 B. Pirogovskaya, 119021 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eslam","family":"Ghazy","sequence":"additional","affiliation":[{"name":"Federal Research Center \u201cFundamentals of Biotechnology\u201d of the Russian Academy of Sciences, Bach Institute of Biochemistry, 33 Leninsky Ave., bld. 2, 119071 Moscow, Russia"},{"name":"Institute of Biochemical Technology and Nanotechnology, Peoples\u2019 Friendship University of Russia (RUDN), 6 Miklukho-Maklaya Street, 117198 Moscow, Russia"},{"name":"Department of Microbiology, Faculty of Pharmacy, Tanta University, Tanta 31111, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Bychkova","sequence":"additional","affiliation":[{"name":"Gause Institute of New Antibiotics, 11 B. Pirogovskaya, 119021 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgy","family":"Zatonsky","sequence":"additional","affiliation":[{"name":"Gause Institute of New Antibiotics, 11 B. Pirogovskaya, 119021 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Grammatikova","sequence":"additional","affiliation":[{"name":"Gause Institute of New Antibiotics, 11 B. Pirogovskaya, 119021 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyubov","family":"Dezhenkova","sequence":"additional","affiliation":[{"name":"Gause Institute of New Antibiotics, 11 B. Pirogovskaya, 119021 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Solovieva","sequence":"additional","affiliation":[{"name":"Gause Institute of New Antibiotics, 11 B. Pirogovskaya, 119021 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Ostroumova","sequence":"additional","affiliation":[{"name":"Institute of Cytology of the Russian Academy of Sciences, 4 Tikhoretsky, 194064 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6595-0811","authenticated-orcid":false,"given":"Andrey","family":"Shchekotikhin","sequence":"additional","affiliation":[{"name":"Gause Institute of New Antibiotics, 11 B. Pirogovskaya, 119021 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1056\/NEJMra1315399","article-title":"Invasive Candidiasis","volume":"373","author":"Kullberg","year":"2015","journal-title":"N. Engl. J. 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