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Novel 5-Substituted 2-(Aylmethylthio)-4-chloro-N-(5-aryl-1,2,4-triazin-3-yl)benzenesulfonamides: Synthesis, Molecular Structure, Anticancer Activity, Apoptosis-Inducing Activity and Metabolic Stability
Abstract
A series of novel 5-substituted 2-(arylmethylthio)-4-chloro-N-(5-aryl-1,2,4-triazin-3-yl) benzenesulfonamide derivatives 27–60 have been synthesized by the reaction of aminoguanidines with an appropriate phenylglyoxal hydrate in glacial acetic acid. A majority of the compounds showed cytotoxic activity toward the human cancer cell lines HCT-116, HeLa and MCF-7, with IC50 values below 100 M. It was found that for the analogues 36–38 the naphthyl moiety contributed significantly to the anticancer activity. Cytometric analysis of translocation of phosphatidylserine as well as mitochondrial membrane potential and cell cycle revealed that the most active compounds 37 (HCT-116 and HeLa) and 46 (MCF-7) inhibited the proliferation of cells by increasing the number of apoptotic cells. Apoptotic-like, dose dependent changes in morphology of cell lines were also noticed after treatment with 37 and 46. Moreover, triazines 37 and 46 induced caspase activity in the HCT-116, HeLa and MCF-7 cell lines. Selected compounds were tested for metabolic stability in the presence of pooled human liver microsomes and NADPH, both R2 and Ar = 4-CF3-C6H4 moiety in 2-(R2-methylthio)-N-(5-aryl-1,2,4-triazin-3-yl)benzenesulfonamides simultaneously increased metabolic stability. The results pointed to 37 as a hit compound with a good cytotoxicity against HCT-116 (IC50 = 36 uM), HeLa (IC50 = 34 uM) cell lines, apoptosis-inducing activity and moderate metabolic stability.
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Authors (10)
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Beata Żołnowska
- Gdański Unwersytet Medyczny Katedra Chemii Organicznej
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Jarosław Sławiński
- Gdański Unwersytet Medyczny Katedra Chemii Organicznej
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Aneta Pogorzelska
- Gdański Unwersytet Medyczny Katedra Chemii Organicznej
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Krzysztof Szafrański dr
- Gdański Unwersytet Medyczny Katedra Chemii Organicznej
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Anna Kawiak
- Gdański Unwersytet Medyczny Laboratorium Fizjologii Człowieka
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Grzegorz Stasiłojć
- Gdański Unwersytet Medyczny Zakład Biotechnologii Medycznej
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Mariusz Belka
- Gdański Unwersytet Medyczny Zakład Chemii Farmaceutycznej
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Szymon Ulenberg
- Gdański Unwersytet Medyczny Zakład Chemii Farmaceutycznej
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Tomasz Bączek
- Gdański Unwersytet Medyczny Zakład Chemii Farmaceutycznej
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- Accepted or Published Version
- DOI:
- Digital Object Identifier (open in new tab) 10.3390/molecules21060808
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- Category:
- Articles
- Type:
- artykuł w czasopiśmie wyróżnionym w JCR
- Published in:
-
MOLECULES
no. 21,
edition 6,
pages 1 - 27,
ISSN: 1420-3049 - Language:
- English
- Publication year:
- 2016
- Bibliographic description:
- Żołnowska B., Sławiński J., Pogorzelska A., Szafrański K., Kawiak A., Stasiłojć G., Belka M., Ulenberg S., Bączek T., Chojnacki J.: Novel 5-Substituted 2-(Aylmethylthio)-4-chloro-N-(5-aryl-1,2,4-triazin-3-yl)benzenesulfonamides: Synthesis, Molecular Structure, Anticancer Activity, Apoptosis-Inducing Activity and Metabolic Stability// MOLECULES. -Vol. 21, iss. 6 (2016), s.1-27
- DOI:
- Digital Object Identifier (open in new tab) 10.3390/molecules21060808
- Verified by:
- Gdańsk University of Technology
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