{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:45:35Z","timestamp":1760060735563,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Cutaneous melanoma (CM) is widely regarded as the most aggressive form of skin cancer worldwide, showing a rising global incidence. It develops from the uncontrolled transformation of pigment-producing melanocytes. The aim of this study is to characterize the cytotoxic and anti-proliferative properties of two 1-(2-aryl-adamantyl)piperazine derivatives, 6 and 7, with a specific emphasis on their impact on melanoma cells. Both compounds are synthesized based on the adamantane core structure which increases drug-like properties of the lead compound phencyclidine I, without increasing toxicity. Materials and Methods: This study describes concentration-dependent effects on cell viability and clonogenicity. Results: SRB assays, clonogenic (long-term) assays, and scratch assays reveal a significant anticancer activity of these two agents at low \u03bc\u039c levels with a selective activity against melanoma cells. Furthermore, Western blot experiments indicate that both 6 and 7 induce LC3 accumulation, procaspase 3 decrease, and PARP cleavage, suggesting the implication of multiple death pathways in their anticancer mechanism of action. Conclusions: This study sheds light on the in vitro anticancer potential of two novel 1-(2-aryl-2-adamantyl)piperazine derivatives. It highlights their differential activity against melanoma and emphasizes their potential as lead candidates for further therapeutic exploration.<\/jats:p>","DOI":"10.3390\/medicina61101731","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T15:54:54Z","timestamp":1758642894000},"page":"1731","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel 1-(2-Aryl-2-adamantyl)piperazine Derivatives Exhibit In Vitro Anticancer Activity Across Various Human Cancer Cell Lines, with Selective Efficacy Against Melanoma"],"prefix":"10.3390","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7058-5257","authenticated-orcid":false,"given":"Irida","family":"Papapostolou","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, Faculty of Medicine, University of Bern, 3012 Bern, Switzerland"},{"name":"Department of Pharmacology, Faculty of Medicine, Health Sciences School, University of Thessaly, 41500 Larissa, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5947-9971","authenticated-orcid":false,"given":"Evangelia","family":"Sereti","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Health Sciences School, University of Thessaly, 41500 Larissa, Greece"},{"name":"Department of Translational Medicine, Faculty of Medicine, Lund University, 21428 Malm\u00f6, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stavroula","family":"Chatira","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Health Sciences School, University of Thessaly, 41500 Larissa, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikos","family":"Sakellaridis","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Health Sciences School, University of Thessaly, 41500 Larissa, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1239-8901","authenticated-orcid":false,"given":"George","family":"Fytas","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, 15772 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9442-5186","authenticated-orcid":false,"given":"Grigoris","family":"Zoidis","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, 15772 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7481-9148","authenticated-orcid":false,"given":"Konstantinos","family":"Dimas","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Health Sciences School, University of Thessaly, 41500 Larissa, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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