Synthesis of 3-(2-Alkylthio-4-chloro-5-methylbenzenesulfonyl)-2-(1-phenyl-3-arylprop-2-enylideneamino)guanidine Derivatives with Pro-Apoptotic Activity against Cancer Cells
The untypical course of reaction between chalcones and benzenesulfonylaminoguanidines led to the new 3-(2-alkylthio-4-chloro-5-methylbenzenesulfonyl)-2-(1-phenyl-3-arylprop-2-enylideneamino)guanidine derivatives <b>8</b>–<b>33</b>. The new compounds were tested in vitro for t...
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/5/4436 |
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| author | Aneta Pogorzelska Jarosław Sławiński Anna Kawiak Grzegorz Stasiłojć Jarosław Chojnacki |
| author_facet | Aneta Pogorzelska Jarosław Sławiński Anna Kawiak Grzegorz Stasiłojć Jarosław Chojnacki |
| author_sort | Aneta Pogorzelska |
| collection | DOAJ |
| description | The untypical course of reaction between chalcones and benzenesulfonylaminoguanidines led to the new 3-(2-alkylthio-4-chloro-5-methylbenzenesulfonyl)-2-(1-phenyl-3-arylprop-2-enylideneamino)guanidine derivatives <b>8</b>–<b>33</b>. The new compounds were tested in vitro for their impact on the growth of breast cancer cells MCF-7, cervical cancer cells HeLa and colon cancer cells HCT-116 by MTT assay. The results revealed that the activity of derivatives is strongly related to the presence of hydroxy group in the benzene ring at the 3-arylpropylidene fragment. The most cytotoxic compounds <b>20</b> and <b>24</b> displayed mean IC<sub>50</sub> values of 12.8 and 12.7 μM, respectively, against three tested cell lines and were almost 3- and 4-fold more active toward MCF-7 and HCT-116 when compared with non-malignant HaCaT cells. Furthermore, compound <b>24</b> induced apoptosis in cancer cells and caused a decrease of mitochondrial membrane potential as well as an increase of cells in sub-G1 phase in contrast to its inactive analog <b>31</b>. The strongest activity against the most sensitive HCT-116 cell line was found for compound <b>30</b> (IC<sub>50</sub> = 8 μM), which was 11-fold more effective in the growth inhibition of HCT-116 cells than those of HaCaT cells. Based on this fact, the new derivatives may be promising leading structures for the search for agents for the treatment of colon cancer. |
| first_indexed | 2024-03-11T07:23:26Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T07:23:26Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4484fd07da984487905bd32ba67e29042023-11-17T07:48:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01245443610.3390/ijms24054436Synthesis of 3-(2-Alkylthio-4-chloro-5-methylbenzenesulfonyl)-2-(1-phenyl-3-arylprop-2-enylideneamino)guanidine Derivatives with Pro-Apoptotic Activity against Cancer CellsAneta Pogorzelska0Jarosław Sławiński1Anna Kawiak2Grzegorz Stasiłojć3Jarosław Chojnacki4Department of Organic Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, PolandDepartment of Organic Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, PolandDepartment of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Abrahama 58, 80-307 Gdańsk, PolandDepartment of Cell Biology and Immunology, Intercollegiate Faculty of Biotechnology of UG and MUG, Medical University of Gdańsk, Dębinki 1, 80-211 Gdańsk, PolandDepartment of Inorganic Chemistry, Gdańsk University of Technology, Narutowicza 11/12, 80-233 Gdańsk, PolandThe untypical course of reaction between chalcones and benzenesulfonylaminoguanidines led to the new 3-(2-alkylthio-4-chloro-5-methylbenzenesulfonyl)-2-(1-phenyl-3-arylprop-2-enylideneamino)guanidine derivatives <b>8</b>–<b>33</b>. The new compounds were tested in vitro for their impact on the growth of breast cancer cells MCF-7, cervical cancer cells HeLa and colon cancer cells HCT-116 by MTT assay. The results revealed that the activity of derivatives is strongly related to the presence of hydroxy group in the benzene ring at the 3-arylpropylidene fragment. The most cytotoxic compounds <b>20</b> and <b>24</b> displayed mean IC<sub>50</sub> values of 12.8 and 12.7 μM, respectively, against three tested cell lines and were almost 3- and 4-fold more active toward MCF-7 and HCT-116 when compared with non-malignant HaCaT cells. Furthermore, compound <b>24</b> induced apoptosis in cancer cells and caused a decrease of mitochondrial membrane potential as well as an increase of cells in sub-G1 phase in contrast to its inactive analog <b>31</b>. The strongest activity against the most sensitive HCT-116 cell line was found for compound <b>30</b> (IC<sub>50</sub> = 8 μM), which was 11-fold more effective in the growth inhibition of HCT-116 cells than those of HaCaT cells. Based on this fact, the new derivatives may be promising leading structures for the search for agents for the treatment of colon cancer.https://www.mdpi.com/1422-0067/24/5/4436benzenesulfonamidesbenzenesulfonylguanidinesamidrazonesanticancer activitycytotoxicitycell cycle flow cytometry analysis |
| spellingShingle | Aneta Pogorzelska Jarosław Sławiński Anna Kawiak Grzegorz Stasiłojć Jarosław Chojnacki Synthesis of 3-(2-Alkylthio-4-chloro-5-methylbenzenesulfonyl)-2-(1-phenyl-3-arylprop-2-enylideneamino)guanidine Derivatives with Pro-Apoptotic Activity against Cancer Cells International Journal of Molecular Sciences benzenesulfonamides benzenesulfonylguanidines amidrazones anticancer activity cytotoxicity cell cycle flow cytometry analysis |
| title | Synthesis of 3-(2-Alkylthio-4-chloro-5-methylbenzenesulfonyl)-2-(1-phenyl-3-arylprop-2-enylideneamino)guanidine Derivatives with Pro-Apoptotic Activity against Cancer Cells |
| title_full | Synthesis of 3-(2-Alkylthio-4-chloro-5-methylbenzenesulfonyl)-2-(1-phenyl-3-arylprop-2-enylideneamino)guanidine Derivatives with Pro-Apoptotic Activity against Cancer Cells |
| title_fullStr | Synthesis of 3-(2-Alkylthio-4-chloro-5-methylbenzenesulfonyl)-2-(1-phenyl-3-arylprop-2-enylideneamino)guanidine Derivatives with Pro-Apoptotic Activity against Cancer Cells |
| title_full_unstemmed | Synthesis of 3-(2-Alkylthio-4-chloro-5-methylbenzenesulfonyl)-2-(1-phenyl-3-arylprop-2-enylideneamino)guanidine Derivatives with Pro-Apoptotic Activity against Cancer Cells |
| title_short | Synthesis of 3-(2-Alkylthio-4-chloro-5-methylbenzenesulfonyl)-2-(1-phenyl-3-arylprop-2-enylideneamino)guanidine Derivatives with Pro-Apoptotic Activity against Cancer Cells |
| title_sort | synthesis of 3 2 alkylthio 4 chloro 5 methylbenzenesulfonyl 2 1 phenyl 3 arylprop 2 enylideneamino guanidine derivatives with pro apoptotic activity against cancer cells |
| topic | benzenesulfonamides benzenesulfonylguanidines amidrazones anticancer activity cytotoxicity cell cycle flow cytometry analysis |
| url | https://www.mdpi.com/1422-0067/24/5/4436 |
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