Jeleń, M.; Otto-Ślusarczyk, D.; Morak-Młodawska, B.; Struga, M. Novel Tetracyclic Azaphenothiazines with the Quinoline Ring as New Anticancer and Antibacterial Derivatives of Chlorpromazine. Int. J. Mol. Sci.2024, 25, 4148.
Jeleń, M.; Otto-Ślusarczyk, D.; Morak-Młodawska, B.; Struga, M. Novel Tetracyclic Azaphenothiazines with the Quinoline Ring as New Anticancer and Antibacterial Derivatives of Chlorpromazine. Int. J. Mol. Sci. 2024, 25, 4148.
Jeleń, M.; Otto-Ślusarczyk, D.; Morak-Młodawska, B.; Struga, M. Novel Tetracyclic Azaphenothiazines with the Quinoline Ring as New Anticancer and Antibacterial Derivatives of Chlorpromazine. Int. J. Mol. Sci.2024, 25, 4148.
Jeleń, M.; Otto-Ślusarczyk, D.; Morak-Młodawska, B.; Struga, M. Novel Tetracyclic Azaphenothiazines with the Quinoline Ring as New Anticancer and Antibacterial Derivatives of Chlorpromazine. Int. J. Mol. Sci. 2024, 25, 4148.
Abstract
Phenothiazine derivatives are widely studied in various fields such as biology, chemistry, and medicine research because of their pharmaceutical effects. The first reagent that was used suc-cessfully in the treatment of psychosis was a phenthiazine derivative, chlorpromazine. Apart from their activity in neurons, chlorpromazine have also been reported to display anticancer and antibacterial properties. In these studies, we present the synthesis and research on the activ-ity against A549, MDA, MiaPaCa, PC3 and HCT116 cancer cell lines and against S. aureus, S. epi-dermidis, E. coli and P. aeruginosa bacterial strains a series of new tetracyclic chlorpromazine ana-logues containing a quinoline scafford in their structure instead of the benzene ring and various substituents at the thiazine nitrogen. The structure of these novel molecules has been deter-mined by 1H NMR, 13C NMR and HRMS spectral techniques. The seven most active of the twen-ty-four new chlorpromazine analogues tested were selected for study of the mechanism of cyto-toxic action. Their ability to induce apoptosis or necrosis in cancer cells was assessed by flow cytometry analysis. The results obtained confirmed the proapoptotic activity of selected com-pounds, especially in terms of inducing late apoptosis or necrosis in cancer cell lines A549, Mi-aPaCa-2 and HCT-116. Furthermore, studies on the induction of cell cycle arrest suggest that the new chlorpromazine analogues exert antiproliferative effects by inducing cell cycle arrest in the S phase and, consequently, apoptosis.
Chemistry and Materials Science, Medicinal Chemistry
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