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
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 activ...
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MDPI AG
2016-06-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/21/6/808 |
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| author | Beata Żołnowska Jarosław Sławiński Aneta Pogorzelska Krzysztof Szafrański Anna Kawiak Grzegorz Stasiłojć Mariusz Belka Szymon Ulenberg Tomasz Bączek Jarosław Chojnacki |
| author_facet | Beata Żołnowska Jarosław Sławiński Aneta Pogorzelska Krzysztof Szafrański Anna Kawiak Grzegorz Stasiłojć Mariusz Belka Szymon Ulenberg Tomasz Bączek Jarosław Chojnacki |
| author_sort | Beata Żołnowska |
| collection | DOAJ |
| description | 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 μM. 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 μM), HeLa (IC50 = 34 μM) cell lines, apoptosis-inducing activity and moderate metabolic stability. |
| first_indexed | 2024-12-21T02:47:08Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-21T02:47:08Z |
| publishDate | 2016-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-989ecdc9655f4b0c8337523c6838227c2022-12-21T19:18:32ZengMDPI AGMolecules1420-30492016-06-0121680810.3390/molecules21060808molecules21060808Novel 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 StabilityBeata Żołnowska0Jarosław Sławiński1Aneta Pogorzelska2Krzysztof Szafrański3Anna Kawiak4Grzegorz Stasiłojć5Mariusz Belka6Szymon Ulenberg7Tomasz Bączek8Jarosław Chojnacki9Department of Organic Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, Gdańsk 80-416, PolandDepartment of Organic Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, Gdańsk 80-416, PolandDepartment of Organic Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, Gdańsk 80-416, PolandDepartment of Organic Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, Gdańsk 80-416, PolandDepartment of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, ul. Abrahama 58, Gdańsk 80-307, PolandLaboratory of Cell Biology, Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology UG-MUG, Medical University of Gdańsk, ul. Dębinki 1, Gdańsk 80-211, PolandDepartment of Pharmaceutical Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, Gdańsk 80-416, PolandDepartment of Pharmaceutical Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, Gdańsk 80-416, PolandDepartment of Pharmaceutical Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, Gdańsk 80-416, PolandDepartment of Inorganic Chemistry, Gdańsk University of Technology, Narutowicza 11/12, Gdańsk 80-233, PolandA 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 μM. 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 μM), HeLa (IC50 = 34 μM) cell lines, apoptosis-inducing activity and moderate metabolic stability.http://www.mdpi.com/1420-3049/21/6/808sulfonamidesynthesismetabolic stabilityanticancerapoptosismitochondrial membrane potential |
| spellingShingle | Beata Żołnowska Jarosław Sławiński Aneta Pogorzelska Krzysztof Szafrański Anna Kawiak Grzegorz Stasiłojć Mariusz Belka Szymon Ulenberg Tomasz Bączek Jarosław Chojnacki 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 sulfonamide synthesis metabolic stability anticancer apoptosis mitochondrial membrane potential |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | sulfonamide synthesis metabolic stability anticancer apoptosis mitochondrial membrane potential |
| url | http://www.mdpi.com/1420-3049/21/6/808 |
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