In this paper, we describe a new method for synthesizing hybrid combinations of 1,2,3-triazoles with a tetracyclic quinobenzothiazinium system. The developed approach allowed for the production of a series of new azaphenothiazine derivatives with the 1,2,3-triazole system in different positions of the benzene ring. In practice, the methodology consists of the reaction of triazole aniline derivatives with thioquinanthrenediinium bis-chloride. The structure of the products was determined by 1H-NMR, 13C-NMR spectroscopy, and HR-MS spectrometry, respectively. Moreover, the spatial structure of the molecule and the arrangement of molecules in the crystal (unit cell) were determined by X-ray crystallography. The anticancer activity profiles of the synthesized compounds were tested in vitro against human cancer cells of the A549, SNB-19, and T47D lines and the normal NHDF cell line. Additional tests of antibacterial activity against methicillin-sensitive and methicillin-resistant staphylococci, vancomycin-sensitive and vancomycin-resistant enterococci, and two mycobacterial strains were also performed. In fact, the dependence of anticancer and antibacterial activity on the substituent type and its position in the quinobenzothiazinium system was observed. Furthermore, the distance-guided property evaluation was performed using principal component analysis (PCA) and hierarchical clustering analysis (HCA) on the pool of the calculated descriptors. Finally, the theoretically approximated partition coefficients (clogP) were (inter-)correlated with each other and cross-compared with the empirically specified logPTLC parameters.

Department of Analytical Chemistry Faculty of Natural Sciences Comenius University Ilkovicova 6 842 15 Bratislava Slovakia

Department of Cell Biology Faculty of Pharmaceutical Sciences in Sosnowiec Medical University of Silesia Jedności 9 41 200 Sosnowiec Poland

Department of Infectious Diseases and Microbiology Faculty of Veterinary Medicine University of Veterinary Sciences Brno Palackeho tr 1946 1 612 42 Brno Czech Republic

Department of Organic Chemistry Faculty of Pharmaceutical Sciences in Sosnowiec Medical University of Silesia Jagiellońska 4 41 200 Sosnowiec Poland

Faculty of Mathematics and Natural Sciences Cardinal Stefan Wyszyński University K Woycickiego 1 3 01 938 Warszawa Poland

Institute of Chemistry University of Silesia Szkolna 9 40 006 Katowice Poland

Institute of Neuroimmunology Slovak Academy of Sciences Dubravska Cesta 9 845 10 Bratislava Slovakia

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