Synthesis, Biological Evaluation and Stability Studies of Some Novel Aza-Acridine Aminoderivatives
Maria Karelou,
Vasileios Kourafalos,
Athanasia P. Tragomalou,
Panagiotis Marakos,
Nicole Pouli,
Ourania E. Tsitsilonis,
Evangelos Gikas,
Ioannis K. Kostakis
Affiliations
Maria Karelou
Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece
Vasileios Kourafalos
Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece
Athanasia P. Tragomalou
Section of Animal & Human Physiology, Department of Biology, National & Kapodistrian University of Athens, Panepistimiopolis, Ilissia, 15771 Athens, Greece
Panagiotis Marakos
Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece
Nicole Pouli
Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece
Ourania E. Tsitsilonis
Section of Animal & Human Physiology, Department of Biology, National & Kapodistrian University of Athens, Panepistimiopolis, Ilissia, 15771 Athens, Greece
Evangelos Gikas
Laboratory of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece
Ioannis K. Kostakis
Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece
Several new amino-substituted aza-acridine derivatives bearing a basic side chain have been designed and synthesized. The antiproliferative activity of the target compounds has been evaluated against three cancer cell lines—namely HCT-116 (colorectal), the uterine sarcoma MES-SA, and its doxorubicin-resistant variant MES-SA/Dx5. A limited number of the new acridines showed marginal cytotoxicity against the tested cell lines; nevertheless, these analogues possessed a similar substitution pattern. The moderate biological activity of these derivatives was attributed to their instability in aqueous media, which has been studied by mass spectrometry and computational chemistry experiments at the density functional level of theory (DFT).
