title: New adamantane phenylalkylamines with σ-receptor binding affinity and anticancer activity, associated with putative antagonism of neuropathic pain.
abstract: The synthesis of the adamantane phenylalkylamines 2a-d, 3a-c, and 4a-e is described. These compounds exhibited significant antiproliferative activity, in vitro, against eight cancer cell lines tested. The σ(1), σ(2), and sodium channel binding affinities of compounds 2a, 3a, 4a, and 4c-e were investigated. The most interesting analogue, 4a, exhibited significant in vivo anticancer profile on pancreas, prostate, leukemia, and ovarian cancer cell line xenografts together with apoptosis and caspase-3 activation. Inhibition of the cancer cells cycle at the sub-G1 level was also obtained with 4a. Finally, encouraging results were observed with 4a in vivo on mice, suggesting putative antimetastatic and analgesic activities of this compound.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, Panepistimioupoli-Zografou, 15771 Athens, Greece.
authors.forename: Stefanos
authors.initials: S
authors.lastname: Riganas
authors.forename: Ioannis
authors.initials: I
authors.lastname: Papanastasiou
authors.forename: George B
authors.initials: GB
authors.lastname: Foscolos
authors.forename: Andrew
authors.initials: A
authors.lastname: Tsotinis
authors.forename: Guillaume
authors.initials: G
authors.lastname: Serin
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Mirjolet
authors.forename: Kostas
authors.initials: K
authors.lastname: Dimas
authors.forename: Vassilios N
authors.initials: VN
authors.lastname: Kourafalos
authors.forename: Andreas
authors.initials: A
authors.lastname: Eleutheriades
authors.forename: Vassilios I
authors.initials: VI
authors.lastname: Moutsos
authors.forename: Humaira
authors.initials: H
authors.lastname: Khan
authors.forename: Stavroula
authors.initials: S
authors.lastname: Georgakopoulou
authors.forename: Angeliki
authors.initials: A
authors.lastname: Zaniou
authors.forename: Margarita
authors.initials: M
authors.lastname: Prassa
authors.forename: Maria
authors.initials: M
authors.lastname: Theodoropoulou
authors.forename: Athanasios
authors.initials: A
authors.lastname: Mantelas
authors.forename: Stavroula
authors.initials: S
authors.lastname: Pondiki
authors.forename: Alexandre
authors.initials: A
authors.lastname: Vamvakides
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D015394:Molecular Structure; D009437:Neuralgia / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010880:Piperidines / Q000138:chemical synthesis / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011485:Protein Binding; D017480:Receptors, sigma / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: C577960:1-methyl-4-(3-(4-(alpha-(1-tricyclo(3.3.1.1(3,7))decyl)phenylmethyl)phenyl)propyl)piperazine; D000970:Antineoplastic Agents; D010880:Piperidines; D017480:Receptors, sigma; D053148:Caspase 3; D000218:Adamantane