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Novel 2-alkythio-4-chloro-N-[imino(heteroaryl)methyl]benzenesulfonamide Derivatives: Synthesis, Molecular Structure, Anticancer Activity and Metabolic Stability
Abstract
A series of novel 2-alkythio-4-chloro-N-[imino-(heteroaryl)methyl]benzenesulfonamide derivatives, 8–24, were synthesized in the reaction of the N-(benzenesulfonyl)cyanamide potassium salts 1–7 with the appropriate mercaptoheterocycles. All the synthesized compounds were evaluated for their anticancer activity in HeLa, HCT-116 and MCF-7 cell lines. The most promising compounds, 11–13, molecular hybrids containing benzenesulfonamide and imidazole moieties, selectively showed a high cytotoxic effect in HeLa cancer cells (IC50: 6–7 uM) and exhibited about three times less cytotoxicity against the non-tumor cell line HaCaT cells (IC50: 18–20 uM). It was found that the anti-proliferative effects of 11, 12 and 13 were associated with their ability to induce apoptosis in HeLa cells. The compounds increased the early apoptotic population of cells, elevated the percentage of cells in the sub-G1 phase of the cell cycle and induced apoptosis through caspase activation in HeLa cells. For the most active compounds, susceptibility to undergo first-phase oxidation reactions in human liver microsomes was assessed. The results of the in vitro metabolic stability experiments indicated values of the factor t12 for 11–13 in the range of 9.1–20.3 min and suggested the hypothetical oxidation of these compounds to sulfenic and subsequently sulfinic acids as metabolites.
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Authors (6)
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Beata Żołnowska
- Medical University of Gdańsk
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Jarosław Sławiński
- Medical University of Gdańsk
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Mariusz Belka
- Medical University of Gdańsk
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Tomasz Baczek
- Medical University of Gdańsk
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Anna Kawiak
- Intercollegiate Faculty of Biotechnology
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- Accepted or Published Version
- DOI:
- Digital Object Identifier (open in new tab) 10.3390/ijms24119768
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- Category:
- Articles
- Type:
- artykuły w czasopismach
- Published in:
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
no. 24,
ISSN: 1661-6596 - Language:
- English
- Publication year:
- 2023
- Bibliographic description:
- Żołnowska B., Sławiński J., Belka M., Baczek T., Chojnacki J., Kawiak A.: Novel 2-alkythio-4-chloro-N-[imino(heteroaryl)methyl]benzenesulfonamide Derivatives: Synthesis, Molecular Structure, Anticancer Activity and Metabolic Stability// INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES -Vol. 24,iss. 11 (2023), s.9768-
- DOI:
- Digital Object Identifier (open in new tab) 10.3390/ijms24119768
- Sources of funding:
-
- COST_FREE
- Verified by:
- Gdańsk University of Technology
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