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New N-benzenesulfonylguanidine derivatives and their selective growth inhibition of human breast cancer cell line MCF-7 and colon carcinoma HCT-116
* 1 , 1 , 2
1  Medical University of Gdansk, Department of Organic Chemistry
2  Intercollegiate Faculty of Biotechnology UG-MUG, Department of Biotechnology
Academic Editor: Alfredo Berzal-Herranz


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 1-4 which were transformed into 1-(2-alkylthio-4-chloro-5-methylbenzenesulfonyl)-3-[(2-chloroacetyl)amino]guanidines 5-8 by a reaction with chloroacetyl chloride. In the next step, the derivatives 5-8 were reacted with potassium thiocyanate yielding 1-(2-alkylthio-4-chloro-5-methylbenzenesulfonyl)-3-(2-imino-4-oxothiazolidine-3-yl)guanidines 9-12.

The synthesized derivatives 5−12 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 5-8 inhibit the growth of cancer cells stronger than derivatives 9-12. The selective cytotoxic effect against HCT-116 cells was found for benzenesulfonylguanidine 6 containing 2-(trifluoromethyl)benzylthio group at position 2 of benzenesulfonyl scaffold. The IC50 value was 13 μM, while IC50 for HaCaT cells was 48 μM. Good selectivity was also observed for compound 7, with 2-chloromethylbenzylthio substituent, against HCT-116 and MCF-7 cells (IC50 = 12 and 19 μM, respectively for HCT-116 and MCF-7 cells, IC50 = 47 μM for HaCaT cells). Among compounds 9-12, only compound 9 showed moderate but selective cytotoxicity against MCF-7 cells, with IC50 = 18 μM compared with IC50 = 54 μM for HaCaT cells.

Keywords: sulfonamides, benzenesulfonylguanidines, cytotoxic activity, anticancer