Biophysical Evaluation and In Vitro Controlled Release of Two Isomeric Adamantane Phenylalkylamines with Antiproliferative/Anticancer and Analgesic Activity
Marilena Vlachou,
Angeliki-Sofia Foscolos,
Angeliki Siamidi,
Angeliki Syriopoulou,
Nikitas Georgiou,
Aikaterini Dedeloudi,
Antonis D. Tsiailanis,
Andreas G. Tzakos,
Thomas Mavromoustakos,
Ioannis P. Papanastasiou
Affiliations
Marilena Vlachou
Division of Pharmaceutical Technology, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimioupoli-Zografou, 157 84 Athens, Greece
Angeliki-Sofia Foscolos
Division of Pharmaceutical Chemistry, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimioupoli-Zografou, 157 84 Athens, Greece
Angeliki Siamidi
Division of Pharmaceutical Technology, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimioupoli-Zografou, 157 84 Athens, Greece
Angeliki Syriopoulou
Department of Organic Chemistry, Faculty of Chemistry, National and Kapodistrian University of Athens, Panepistimioupoli-Zografou, 157 71 Athens, Greece
Nikitas Georgiou
Department of Organic Chemistry, Faculty of Chemistry, National and Kapodistrian University of Athens, Panepistimioupoli-Zografou, 157 71 Athens, Greece
Aikaterini Dedeloudi
Division of Pharmaceutical Technology, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimioupoli-Zografou, 157 84 Athens, Greece
Antonis D. Tsiailanis
Section of Organic Chemistry and Biochemistry, Department of Chemistry, University of Ioannina, 451 10 Ioannina, Greece
Andreas G. Tzakos
Section of Organic Chemistry and Biochemistry, Department of Chemistry, University of Ioannina, 451 10 Ioannina, Greece
Thomas Mavromoustakos
Department of Organic Chemistry, Faculty of Chemistry, National and Kapodistrian University of Athens, Panepistimioupoli-Zografou, 157 71 Athens, Greece
Ioannis P. Papanastasiou
Division of Pharmaceutical Chemistry, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimioupoli-Zografou, 157 84 Athens, Greece
The aqueous dissolution profile of the isomeric synthetic adamantane phenylalkylamine hydrochlorides I and II was probed. These adducts have shown significant antiproliferative/anticancer activity associated with an analgesic profile against neuropathic pain. They are both devoid of toxic effects and show appreciable enzymatic human plasma stability. The structures of these two compounds have been elucidated using 2D NMR experiments, which were used to study their predominant conformations. Compound II’s scaffold appeared more flexible, as shown by the NOE spatial interactions between the alkyl bridge chain, the aromatic rings, and the adamantane nucleus. Conversely, compound I appeared very rigid, as it did not share significant NOEs between the aforementioned structural segments. MD simulations confirmed the NOE results. The aqueous dissolution profile of both molecules fits well with their minimum energy conformers’ features, which stem from the NOE data; this was nicely demonstrated, especially in the case of compound II.
