title: Novel 1-(2-aryl-2-adamantyl)piperazine derivatives with antiproliferative activity.
abstract: Novel 1-(2-aryl-2-adamantyl)piperazine derivatives have been synthesized and evaluated in vitro for their antitumor properties against HeLa cervical carcinoma, MDA MB 231 breast cancer, MIA PaCa2 pancreatic cancer, and NCI H1975 non-small cell lung cancer. The parent piperazine 6 was found to exhibit a reasonable activity toward the HeLa and MDA MB 231 tumor cell lines (IC50= 9.2 and 8.4 μΜ, respectively). Concurrent benzene ring C4-fluorination and piperidine acetylation of the piperazino NH of compound 6 resulted in the most active compound 13 of the series in both of the above cell lines (IC50=8.4 and 6.8 μΜ, respectively). Noticeably, compounds 6 and 13 exhibited a significantly low cytotoxicity level over the normal human cells HUVEC (Human Umbilical Vein Endothelial Cells) and NHDF (Normal Human Dermal Fibroblasts).
authors.affiliation: School of Health Sciences, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Panepistimioupoli-Zografou, GR-15784 Athens, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Fytas
authors.affiliation: School of Health Sciences, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Panepistimioupoli-Zografou, GR-15784 Athens, Greece.
authors.forename: Grigoris
authors.initials: G
authors.lastname: Zoidis
authors.affiliation: School of Health Sciences, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Panepistimioupoli-Zografou, GR-15784 Athens, Greece.
authors.forename: Andrew
authors.initials: A
authors.lastname: Tsotinis
authors.affiliation: School of Health Sciences, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Panepistimioupoli-Zografou, GR-15784 Athens, Greece. Electronic address: gfytas@pharm.uoa.gr.
authors.forename: George
authors.initials: G
authors.lastname: Fytas
authors.affiliation: Institute of Pharmaceutical Sciences, King's College London, Britannia House, 7 Trinity Street, London SE1 1DB, UK.
authors.forename: Mohsin A
authors.initials: MA
authors.lastname: Khan
authors.affiliation: Institute of Pharmaceutical Sciences, King's College London, Britannia House, 7 Trinity Street, London SE1 1DB, UK.
authors.forename: Samar
authors.initials: S
authors.lastname: Akhtar
authors.affiliation: Institute of Pharmaceutical Sciences, King's College London, Britannia House, 7 Trinity Street, London SE1 1DB, UK.
authors.forename: Khondaker M
authors.initials: KM
authors.lastname: Rahman
authors.affiliation: Institute of Pharmaceutical Sciences, King's College London, Britannia House, 7 Trinity Street, London SE1 1DB, UK.
authors.forename: David E
authors.initials: DE
authors.lastname: Thurston
mesh_terms: D000218:Adamantane / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D006367:HeLa Cells; D006801:Humans; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D017480:Receptors, sigma / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D010879:Piperazines; D017480:Receptors, sigma; D000077489:Piperazine; D000218:Adamantane
keywords: 1-(2-aryl-2-adamantyl)piperazines; In vitro antiproliferative activity; N-Boc deprotection; NMR; σ1, σ2-Binding affinity