Towards Anticancer and Antibacterial Agents: Design and Synthesis of 1,2,3-Triazol-quinobenzothiazine Derivatives

Abstract

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.

Critical view on antimicrobial, antibiofilm and cytotoxic activities of quinazolin-4(3H)-one derived schiff bases and their Cu(II) complexes

“…A description of the synthesis of individual compounds, their characterization and a description of the used individual biological tests is given in detail in Supplementary Materials. However, methods described in previous papers [ 32 , 57 , [66] , [67] , [68] , [69] ] were used to prepare the discussed quinazolin-4-one Schiff bases, and recently described methods were used to determine antimicrobial effectivity/cytotoxicity [ 19 , 25 , 26 , 47 , 48 , 51 , [70] , [71] ] of all the investigated derivatives as well as for PET inhibitory activity in spinach chloroplasts [ 44 , 46 , 47 , 72 , 73 ].…”

“…The authors have long been engaged in the study of various types of heterocycles [ 3 , [15] , [16] , [17] , [18] , [19] ], primarily as anti-infective and anti-cancer agents with the aim of obtaining substances with dual (anti-cancer + antibacterial) activity [ [20] , [21] , [22] , [23] , [24] , [25] , [26] ], because such therapeutics are particularly advantageous in the treatment of oncological patients who have drug-suppressed immunity and for whom even banal infections and opportunistic pathogens are a threat. So impressed with the global interest in quinazolin-4(3 H )-ones as antibacterial compounds [ 4 , [27] , [28] , [29] , [30] , [31] ], the previously described anticancer 2,3-disubstituted-quinazolin-4(3 H )-one derived Schiff bases [ 32 , 33 ] were screened for their antimicrobial activity, and their cytotoxic potential was tested against the human monocytic leukemia cell line THP-1 and thus the spectrum of cytotoxic activities published earlier [ 32 , 33 ] was extended to another line.…”