Our previous research for biological properties of 2-mercaptobenzenesulfonamides (MBSA) has revealed the significant anticancer activity of a series of N'-(2-benzylthiobenzenesulfonyl)-1H-pyrazole-1-amidine - the MBSA derivatives [1]. Currently, we report on the novel series of N'-(2-alkylthio-4-chloro-5-methylbenzenesulfonyl)-3-R²-5-phenyl-1H-pyrazole-1-amidine exhibiting even higher in vitro activity against different type of human tumors. As presented in the scheme below, the synthesis of the desired derivatives were achieved by reacting of the corresponding 3-amino-2-(benzenesulfonyl)guanidines (1-5) [2,3,4] with either ketone or acetal to give 1-(1-R²-3-phenylprop-2-ynylideneamino)guanidines (6-15) which were then converted to the N'-(2-alkylthio-4-chloro-5-methylbenzenesulfonyl)-3-R²-5-phenyl-1H-pyrazole-1-amidines (16-25). The structure of the obtained compounds was confirmed by elemental analyses, IR, ¹H and ¹³C NMR spectroscopy and X-ray crystallography.

 Anticancer in vitro screening was performed at the Department of Biotechnology, Intercollegiate Faculty of Biotechnology UG-MUG with using three cancer cell lines. Some of them were tested at the National Cancer Institute (USA) using 60 cell lines derived from 9 types of human tumors. The obtained results showed the high anticancer activity of the tested compounds. The distinctive derivative, i.e. N'-(2-benzylthio-4-chloro-5-methylbenzenesulfonyl)-5-phenyl-1H-pyrazole-1-amidine showed remarkable activity against 17 of human tumor cell lines representing leukemia, lung, colon, melanoma, ovarian, renal and breast at low nanomolar GI₅₀ level in the range of 265 – 870 nM, whereas for the other cell lines GI₅₀ were in the range of 1.16 - 3.15 µM.

This project was financed by National Science Centre (NCN) based on the decision number DEC-2013/09/B/NZ7/00048.

References:

1. Sławiński J., Brożewicz K., Fruzinski A., Główka M.L., Heterocycles, 83, 1093 (2011).

2. Sławiński J., Polish J. Chem., 75, 1309 (2001). 

3. Sławiński J., Bednarski P., Grünert R., Reszka P., Polish J. Chem., 77, 53 (2003).

4. Żołnowska B., Sławiński J., Pogorzelska A. et al., Eur. J. Med. Chem., 71, 135 (2014).

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