New <i>N</i>-Benzenesulfonylguanidine Derivatives and Their Selective Growth Inhibition of Human Breast Cancer Cell Line MCF-7 and Colon Carcinoma HCT-116
Our previous research proved that benzenesulfonylguanidine derivatives display significant cytotoxic activity against human cancer cells. Here, we describe new 1-(2-alkylthio-4-chloro-5-methylbenzenesulfonyl)guanidines with cytotoxic activity against HCT-116 and MCF-7 cells. The planned derivatives...
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MDPI AG
2022-11-01
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| author | Aneta Pogorzelska Jarosław Sławiński Anna Kawiak |
| author_facet | Aneta Pogorzelska Jarosław Sławiński Anna Kawiak |
| author_sort | Aneta Pogorzelska |
| collection | DOAJ |
| description | Our previous research proved that benzenesulfonylguanidine derivatives display significant cytotoxic activity against human cancer cells. Here, we describe new 1-(2-alkylthio-4-chloro-5-methylbenzenesulfonyl)guanidines with cytotoxic activity against HCT-116 and MCF-7 cells. The planned derivatives were obtained by a two-step synthesis. The starting substrates were 1-(2-alkylthio-4-chloro-5-methyl)benzenesulfonyl)-3-aminoguanidines <b>1</b>–<b>4,</b> which were transformed into 1-(2-alkylthio-4-chloro-5-methylbenzenesulfonyl)-3-[(2-chloroacetyl)amino]guanidines <b>5–8</b> by a reaction with chloroacetyl chloride. In the next step, the derivatives <b>5</b>–<b>8</b> were reacted with potassium thiocyanate, yielding 1-(2-alkylthio-4-chloro-5-methylbenzenesulfonyl)-3-(2-imino-4-oxothiazolidine-3-yl)guanidines <b>9</b>–<b>12</b>. The synthesized derivatives <b>5</b>–<b>12</b> were evaluated in vitro by MTT assays for their activity against three human cancer cell lines: colon cancer HCT-116, breast cancer MCF-7, and cervical cancer HeLa. The activity against non-cancerous human epidermal keratinocyte line HaCaT was also examined. The data indicate that compounds <b>5</b>–<b>8</b> inhibit the growth of cancer cells more strongly than derivatives <b>9</b>–<b>12</b>. The selective cytotoxic effect against HCT-116 cells was found for benzenesulfonylguanidine <b>6</b> containing a 2-(trifluoromethyl)benzylthio group at position two of the benzenesulfonyl scaffold. The IC<sub>50</sub> value was 13 μM, while IC<sub>50</sub> for HaCaT cells, it was 48 μM. Good selectivity was also observed for compound <b>7</b>, with a 2-chloromethylbenzylthio substituent, against HCT-116 and MCF-7 cells (IC<sub>50</sub> = 12 and 19 μM, respectively, for HCT-116 and MCF-7 cells, IC<sub>50</sub> = 47 μM for HaCaT cells). Among compounds <b>9</b>–<b>12</b>, only compound <b>9</b> showed moderate but selective cytotoxicity against MCF-7 cells, with IC<sub>50</sub> = 18 μM compared with IC<sub>50</sub> = 54 μM for HaCaT cells. |
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| spelling | doaj.art-b6abef276378415b93b196341cb487fb2023-11-17T12:57:28ZengMDPI AGMedical Sciences Forum2673-99922022-11-011414910.3390/ECMC2022-13281New <i>N</i>-Benzenesulfonylguanidine Derivatives and Their Selective Growth Inhibition of Human Breast Cancer Cell Line MCF-7 and Colon Carcinoma HCT-116Aneta Pogorzelska0Jarosław Sławiński1Anna Kawiak2Department of Organic Chemistry, Medical University of Gdansk, 80-416 Gdansk, PolandDepartment of Organic Chemistry, Medical University of Gdansk, 80-416 Gdansk, PolandDepartment of Biotechnology, Intercollegiate Faculty of Biotechnology UG-MUG, 80-307 Gdansk, PolandOur previous research proved that benzenesulfonylguanidine derivatives display significant cytotoxic activity against human cancer cells. Here, we describe new 1-(2-alkylthio-4-chloro-5-methylbenzenesulfonyl)guanidines with cytotoxic activity against HCT-116 and MCF-7 cells. The planned derivatives were obtained by a two-step synthesis. The starting substrates were 1-(2-alkylthio-4-chloro-5-methyl)benzenesulfonyl)-3-aminoguanidines <b>1</b>–<b>4,</b> which were transformed into 1-(2-alkylthio-4-chloro-5-methylbenzenesulfonyl)-3-[(2-chloroacetyl)amino]guanidines <b>5–8</b> by a reaction with chloroacetyl chloride. In the next step, the derivatives <b>5</b>–<b>8</b> were reacted with potassium thiocyanate, yielding 1-(2-alkylthio-4-chloro-5-methylbenzenesulfonyl)-3-(2-imino-4-oxothiazolidine-3-yl)guanidines <b>9</b>–<b>12</b>. The synthesized derivatives <b>5</b>–<b>12</b> were evaluated in vitro by MTT assays for their activity against three human cancer cell lines: colon cancer HCT-116, breast cancer MCF-7, and cervical cancer HeLa. The activity against non-cancerous human epidermal keratinocyte line HaCaT was also examined. The data indicate that compounds <b>5</b>–<b>8</b> inhibit the growth of cancer cells more strongly than derivatives <b>9</b>–<b>12</b>. The selective cytotoxic effect against HCT-116 cells was found for benzenesulfonylguanidine <b>6</b> containing a 2-(trifluoromethyl)benzylthio group at position two of the benzenesulfonyl scaffold. The IC<sub>50</sub> value was 13 μM, while IC<sub>50</sub> for HaCaT cells, it was 48 μM. Good selectivity was also observed for compound <b>7</b>, with a 2-chloromethylbenzylthio substituent, against HCT-116 and MCF-7 cells (IC<sub>50</sub> = 12 and 19 μM, respectively, for HCT-116 and MCF-7 cells, IC<sub>50</sub> = 47 μM for HaCaT cells). Among compounds <b>9</b>–<b>12</b>, only compound <b>9</b> showed moderate but selective cytotoxicity against MCF-7 cells, with IC<sub>50</sub> = 18 μM compared with IC<sub>50</sub> = 54 μM for HaCaT cells.https://www.mdpi.com/2673-9992/14/1/49sulfonamidesbenzenesulfonylguanidinescytotoxic activityanticancer |
| spellingShingle | Aneta Pogorzelska Jarosław Sławiński Anna Kawiak New <i>N</i>-Benzenesulfonylguanidine Derivatives and Their Selective Growth Inhibition of Human Breast Cancer Cell Line MCF-7 and Colon Carcinoma HCT-116 Medical Sciences Forum sulfonamides benzenesulfonylguanidines cytotoxic activity anticancer |
| title | New <i>N</i>-Benzenesulfonylguanidine Derivatives and Their Selective Growth Inhibition of Human Breast Cancer Cell Line MCF-7 and Colon Carcinoma HCT-116 |
| title_full | New <i>N</i>-Benzenesulfonylguanidine Derivatives and Their Selective Growth Inhibition of Human Breast Cancer Cell Line MCF-7 and Colon Carcinoma HCT-116 |
| title_fullStr | New <i>N</i>-Benzenesulfonylguanidine Derivatives and Their Selective Growth Inhibition of Human Breast Cancer Cell Line MCF-7 and Colon Carcinoma HCT-116 |
| title_full_unstemmed | New <i>N</i>-Benzenesulfonylguanidine Derivatives and Their Selective Growth Inhibition of Human Breast Cancer Cell Line MCF-7 and Colon Carcinoma HCT-116 |
| title_short | New <i>N</i>-Benzenesulfonylguanidine Derivatives and Their Selective Growth Inhibition of Human Breast Cancer Cell Line MCF-7 and Colon Carcinoma HCT-116 |
| title_sort | new i n i benzenesulfonylguanidine derivatives and their selective growth inhibition of human breast cancer cell line mcf 7 and colon carcinoma hct 116 |
| topic | sulfonamides benzenesulfonylguanidines cytotoxic activity anticancer |
| url | https://www.mdpi.com/2673-9992/14/1/49 |
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