{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T23:20:18Z","timestamp":1773271218097,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T00:00:00Z","timestamp":1628035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["PRIN 20173LBZM2"],"award-info":[{"award-number":["PRIN 20173LBZM2"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003500","name":"Universit\u00e0 degli Studi di Padova","doi-asserted-by":"publisher","award":["P-DiSC#04BIRD2019-UNIPD"],"award-info":[{"award-number":["P-DiSC#04BIRD2019-UNIPD"]}],"id":[{"id":"10.13039\/501100003500","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG 15844"],"award-info":[{"award-number":["IG 15844"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["[Institutional Grant, no grant number provided"],"award-info":[{"award-number":["[Institutional Grant, no grant number provided"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Peptaibols, by disturbing the permeability of phospholipid membranes, can overcome anticancer drug resistance, but their natural hydrophobicity hampers their administration. By a green peptide synthesis protocol, we produced two water-soluble analogs of the peptaibol trichogin GA IV, termed K6-Lol and K6-NH2. To reduce production costs, we successfully explored the possibility of changing the naturally occurring 1,2-aminoalcohol leucinol to a C-terminal amide. Peptaibol activity was evaluated in ovarian cancer (OvCa) and Hodgkin lymphoma (HL) cell lines. Peptaibols exerted comparable cytotoxic effects in cancer cell lines that were sensitive\u2014and had acquired resistance\u2014to cisplatin and doxorubicin, as well as in the extrinsic-drug-resistant OvCa 3-dimensional spheroids. Peptaibols, rapidly taken up by tumor cells, deeply penetrated and killed OvCa-spheroids. They led to cell membrane permeabilization and phosphatidylserine exposure and were taken up faster by cancer cells than normal cells. They were resistant to proteolysis and maintained a stable helical structure in the presence of cancer cells. In conclusion, these promising results strongly point out the need for further preclinical evaluation of our peptaibols as new anticancer agents.<\/jats:p>","DOI":"10.3390\/ijms22168362","type":"journal-article","created":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T08:47:52Z","timestamp":1628066872000},"page":"8362","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Analogs of a Natural Peptaibol Exert Anticancer Activity in Both Cisplatin- and Doxorubicin-Resistant Cells and in Multicellular Tumor Spheroids"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5352-5677","authenticated-orcid":false,"given":"Naike","family":"Casagrande","sequence":"first","affiliation":[{"name":"Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cinzia","family":"Borghese","sequence":"additional","affiliation":[{"name":"Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Gabbatore","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Padova, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Morbiato","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Padova, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3302-6499","authenticated-orcid":false,"given":"Marta","family":"De Zotti","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Padova, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4548-3566","authenticated-orcid":false,"given":"Donatella","family":"Aldinucci","sequence":"additional","affiliation":[{"name":"Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2700","DOI":"10.1016\/j.bmc.2017.06.052","article-title":"Therapeutic Peptides: Historical Perspectives, Current Development Trends, and Future Directions","volume":"26","author":"Lau","year":"2018","journal-title":"Bioorg. 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