{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T15:08:32Z","timestamp":1778771312780,"version":"3.51.4"},"reference-count":33,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T00:00:00Z","timestamp":1661731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010653","name":"Masaryk University","doi-asserted-by":"publisher","award":["MUNI\/IGA\/0932\/2021"],"award-info":[{"award-number":["MUNI\/IGA\/0932\/2021"]}],"id":[{"id":"10.13039\/501100010653","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010653","name":"Masaryk University","doi-asserted-by":"publisher","award":["MUNI\/A\/1682\/2020"],"award-info":[{"award-number":["MUNI\/A\/1682\/2020"]}],"id":[{"id":"10.13039\/501100010653","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aminopeptidase N (APN), also known as CD13 antigen or membrane alanyl aminopeptidase, belongs to the M1 family of the MA clan of zinc metallopeptidases. In cancer cells, the inhibition of aminopeptidases including APN causes the phenomenon termed the amino acid deprivation response (AADR), a stress response characterized by the upregulation of amino acid transporters and synthetic enzymes and activation of stress-related pathways such as nuclear factor kB (NFkB) and other pro-apoptotic regulators, which leads to cancer cell death by apoptosis. Recently, APN inhibition has been shown to augment DR4-induced tumor cell death and thus overcome resistance to cancer treatment with DR4-ligand TRAIL, which is available as a recombinant soluble form dulanermin. This implies that APN inhibitors could serve as potential weapons for overcoming cancer treatment resistance. In this study, a series of basically substituted acetamidophenones and the semicarbazones and thiosemicarbazones derived from them were prepared, for which APN inhibitory activity was determined. In addition, a selective anti-proliferative activity against cancer cells expressing APN was demonstrated. Our semicarbazones and thiosemicarbazones are the first compounds of these structural types of Schiff bases that were reported to inhibit not only a zinc-dependent aminopeptidase of the M1 family but also a metalloenzyme.<\/jats:p>","DOI":"10.3390\/ijms23179813","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T21:01:31Z","timestamp":1661806891000},"page":"9813","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Aminopeptidase N Inhibitors as Pointers for Overcoming Antitumor Treatment Resistance"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0255-7967","authenticated-orcid":false,"given":"Old\u0159ich","family":"Farsa","sequence":"first","affiliation":[{"name":"Department of Chemical Drugs, Faculty of Pharmacy, Masaryk University, Palack\u00e9ho 1946\/1, 612 00 Brno, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronika","family":"Ballayov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Chemical Drugs, Faculty of Pharmacy, Masaryk University, Palack\u00e9ho 1946\/1, 612 00 Brno, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radka","family":"\u017d\u00e1\u010dkov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Chemical Drugs, Faculty of Pharmacy, Masaryk University, Palack\u00e9ho 1946\/1, 612 00 Brno, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2265-1528","authenticated-orcid":false,"given":"Peter","family":"Kollar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Masaryk University, Palack\u00e9ho 1946\/1, 612 00 Brno, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2854-511X","authenticated-orcid":false,"given":"Tereza","family":"Kauerov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Masaryk University, Palack\u00e9ho 1946\/1, 612 00 Brno, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Zub\u00e1\u010d","sequence":"additional","affiliation":[{"name":"Department of Chemical Drugs, Faculty of Pharmacy, Masaryk University, Palack\u00e9ho 1946\/1, 612 00 Brno, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,29]]},"reference":[{"key":"ref_1","first-page":"362","article-title":"The moonlighting enzyme CD13: Old and new functions to target","volume":"14","year":"2008","journal-title":"Trends Mol. 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