14-Substituted Diquinothiazines as a New Group of Anticancer Agents
Małgorzata Jeleń,
Krystian Pluta,
Małgorzata Szmielew,
Beata Morak-Młodawska,
Kinga Herman,
Klaudia Giercuszkiewicz,
Anna Kasprzycka,
Magdalena Skonieczna
Affiliations
Małgorzata Jeleń
Department of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, The Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland
Krystian Pluta
Department of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, The Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland
Małgorzata Szmielew
Department of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, The Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland
Beata Morak-Młodawska
Department of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, The Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland
Kinga Herman
Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Faculty of Chemistry, Silesian University of Technology, Krzywoustego Street 4, 44-100 Gliwice, Poland
Klaudia Giercuszkiewicz
Department of Systems Biology and Engineering, The Silesian University of Technology, Akademicka Street 16, 44–100 Gliwice, Poland
Anna Kasprzycka
Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Faculty of Chemistry, Silesian University of Technology, Krzywoustego Street 4, 44-100 Gliwice, Poland
Magdalena Skonieczna
Department of Systems Biology and Engineering, The Silesian University of Technology, Akademicka Street 16, 44–100 Gliwice, Poland
A series of novel double-angularly condensed diquinothiazines with aminoalkyl, amidoalkyl, sulfonamidoalkyl, and substituted phenyl groups was designed, synthesized, and evaluated for their anticancer activity against four selected human tumor cell lines (HTC116, SH-SY5Y, A549, and H1299). The cytotoxicity of the novel diquinothiazines was investigated against BEAS-2B cells. The activities of the compounds were compared to etoposide. Among them, compounds with aminoalkyl and phenyl groups showed excellent broad-spectrum anticancer activity. The most active 14-(methylthiophenyl)diquinothiazine, 3c, showed low cytotoxicity against BEAS-2B cells and high activity against tumor cell lines HTC116, SH-SY5Y, A549, and H1299, with IC50 values of 2.3 µM, 2.7 µM, 17.2 µM, and 2.7 µM, respectively (etopiside 8.6 µM, 3.9 µM, 44.8 µM, and 0.6, respectively). Live long-term microscopic observations of cell survival using the starting molecule M0 were also performed. Flow cytometry showed the proapoptotic effects of the studied diquinothiazines. Inhibition of the cell cycle in the S phase was observed, which is associated with damage to nucleic acids and connected to DNA replication arrest.
