Anticancer Efficacy of Antibacterial Quinobenzothiazines

Kisiel-Nawrot, Ewa; Latocha, Małgorzata; Bąk, Andrzej; Kozik, Violetta; Jampílek, Josef; Zięba, Andrzej

doi:10.3390/app13052886

Cited by 4 publications

(3 citation statements)

References 50 publications

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“…The cytotoxic activity with standard deviation (±std) of the aniline 1,2,3-triazole derivatives 5a,f,h,i. The synthesized 1,2,3-triazole 2a-n quinobenzothiazinium derivatives revealed much higher anticancer activity compared to the previously analyzed quinobenzothiazinium derivatives [7], which emphasized the importance of the 1,2,3-triazole system for the cytotoxic activity of compound 2.…”

Section: In Vitro Cytotoxic Activitymentioning

confidence: 70%

“…C 26 H 22 N 5 OS + Cl -, M r = 487.99, red plate, 0.038 × 0.164 × 0.293 mm, monoclinic, space group Cc, a = 4.4070 (7)…”

Section: X-ray Structural Analysismentioning

confidence: 99%

“…It was revealed that reducing the above length to two carbon atoms changes the activity from neuroleptic to antihistaminic. As a matter of fact, many different phenothiazine derivatives with interesting biological properties, such as anticancer, antibacterial, anti-inflammatory, and antiviral, have been described so far [5][6][7]. The structures of the synthesized derivatives were modified by introducing a variety of substituents to the thiazine nitrogen atom or swapping one or two benzene rings into nitrogen heterocyclic systems, which led to the corresponding azaphenothiazines [8,9].…”

Section: Introductionmentioning

confidence: 99%

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

Kisiel-Nawrot,

Pindjakova,

Latocha

et al. 2023

IJMS

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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.

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Section: In Vitro Cytotoxic Activitymentioning

confidence: 70%

“…C 26 H 22 N 5 OS + Cl -, M r = 487.99, red plate, 0.038 × 0.164 × 0.293 mm, monoclinic, space group Cc, a = 4.4070 (7)…”

Section: X-ray Structural Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Kisiel-Nawrot,

Pindjakova,

Latocha

et al. 2023

IJMS

Self Cite

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Design, Synthesis, and Anticancer and Antibacterial Activities of Quinoline-5-Sulfonamides

Zieba,

Pindjakova,

Latocha

et al. 2024

Molecules

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A series of new unique acetylene derivatives of 8-hydroxy- and 8-methoxyquinoline- 5-sulfonamide 3a–f and 6a–f were prepared by reactions of 8-hydroxy- and 8-methoxyquinoline- 5-sulfonyl chlorides with acetylene derivatives of amine. A series of new hybrid systems containing quinoline and 1,2,3-triazole systems 7a–h were obtained by reactions of acetylene derivatives of quinoline-5-sulfonamide 6a–d with organic azides. The structures of the obtained compounds were confirmed by 1H and 13C NMR spectroscopy and HR-MS spectrometry. The obtained quinoline derivatives 3a–f and 6a–f and 1,2,3-triazole derivatives 7a–h were tested for their anticancer and antimicrobial activity. Human amelanotic melanoma cells (C-32), human breast adenocarcinoma cells (MDA-MB-231), and human lung adenocarcinoma cells (A549) were selected as tested cancer lines, while cytotoxicity was investigated on normal human dermal fibroblasts (HFF-1). All the compounds were also tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and representatives of multidrug-resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis. Only the acetylene derivatives of 8-hydroxyquinoline-5-sulfonamide 3a–f were shown to be biologically active, and 8-hydroxy-N-methyl-N-(prop-2-yn-1-yl)quinoline-5-sulfonamide (3c) showed the highest activity against all three cancer lines and MRSA isolates. Its efficacies were comparable to those of cisplatin/doxorubicin and oxacillin/ciprofloxacin. In the non-cancer HFF-1 line, the compound showed no toxicity up to an IC50 of 100 µM. In additional tests, compound 3c decreased the expression of H3, increased the transcriptional activity of cell cycle regulators (P53 and P21 proteins), and altered the expression of BCL-2 and BAX genes in all cancer lines. The unsubstituted phenolic group at position 8 of the quinoline is the key structural fragment necessary for biological activity.

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Synthesis and Structure of 5-Methyl-9-(trifluoromethyl)-12H-quino[3,4-b][1,4]benzothiazinium Chloride as Anticancer Agent

Zieba,

Kozik,

Suwinska

et al. 2024

Molecules

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In this work, the synthesis, structural analysis and anticancer properties of 5-methyl-9-trifluoromethyl-12H-quino[3,4-b][1,4]benzothiazinium chloride (3) are described. Compound 3 was synthesized by reacting 1-methyl-4-butylthio-3-(benzoylthio)quinolinium chloride with 4-(trifluoromethyl)aniline, respectively. The structure of the resulting product was determined using 1H-NMR and 13C-NMR spectroscopy as well as HR-MS spectrometry. The spatial geometry of agent 3 and the arrangement of molecules in the crystal (unit cell) were also confirmed using X-ray diffraction. The tetracyclic quinobenzothiazinium system is fairly planar because the dihedral angle between the planes formed by the benzene ring and the quinoline system is 173.47°. In order to obtain insight into the electronic charge distribution of the investigated molecule, electronic structure calculations employing the Density Functional Theory (DFT) were performed. Moreover, antiproliferative activity against a set of pancreatic cancer cell lines was tested, with compound 3 showing IC50 values against human primary pancreatic adenocarcinoma BxPC-3 and human epithelioid pancreatic carcinoma Panc-1 of 0.051 µM and 0.066 µM, respectively. The IC50 value of cytotoxicity/cell viability of the investigated compound assessed on normal human lung fibroblasts WI38 was 0.36 µM.

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Anticancer Efficacy of Antibacterial Quinobenzothiazines

Cited by 4 publications

References 50 publications

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

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

Design, Synthesis, and Anticancer and Antibacterial Activities of Quinoline-5-Sulfonamides

Synthesis and Structure of 5-Methyl-9-(trifluoromethyl)-12H-quino[3,4-b][1,4]benzothiazinium Chloride as Anticancer Agent

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