Novel 1-(2-Aryl-2-adamantyl)piperazine Derivatives Exhibit In Vitro Anticancer Activity Across Various Human Cancer Cell Lines, with Selective Efficacy Against Melanoma
(2025) In Medicina (Lithuania) 61(10).- Abstract
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:... (More)
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 μΜ 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.
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- author
- Papapostolou, Irida ; Sereti, Evangelia LU ; Chatira, Stavroula ; Sakellaridis, Nikos ; Fytas, George ; Zoidis, Grigoris and Dimas, Konstantinos
- organization
- publishing date
- 2025-10
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- 1-(2-aryl-2-adamantyl)piperazine derivatives, apoptosis, autophagy, melanoma, sigma ligands, sigma receptors
- in
- Medicina (Lithuania)
- volume
- 61
- issue
- 10
- article number
- 1731
- publisher
- MDPI AG
- external identifiers
-
- pmid:41155718
- scopus:105020067240
- ISSN
- 1010-660X
- DOI
- 10.3390/medicina61101731
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2025 by the authors.
- id
- 22297e1c-47bb-4c44-83f6-6c6b679fdcee
- date added to LUP
- 2025-12-17 14:14:51
- date last changed
- 2025-12-18 06:37:27
@article{22297e1c-47bb-4c44-83f6-6c6b679fdcee,
abstract = {{<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 μΜ 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.</p>}},
author = {{Papapostolou, Irida and Sereti, Evangelia and Chatira, Stavroula and Sakellaridis, Nikos and Fytas, George and Zoidis, Grigoris and Dimas, Konstantinos}},
issn = {{1010-660X}},
keywords = {{1-(2-aryl-2-adamantyl)piperazine derivatives; apoptosis; autophagy; melanoma; sigma ligands; sigma receptors}},
language = {{eng}},
number = {{10}},
publisher = {{MDPI AG}},
series = {{Medicina (Lithuania)}},
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}},
url = {{http://dx.doi.org/10.3390/medicina61101731}},
doi = {{10.3390/medicina61101731}},
volume = {{61}},
year = {{2025}},
}