N-Acylation of sulfonamides is an important transformation used for lead optimization as well as lead generation. N-Acylsulfonamides have diverse pharmacological activities including antiproliferative activity as cyclooxygenase [1], tubulin [2] and cyclin-dependent kinases [3] inhibitors. We have recently reported that some N-acylsulfonamides exhibit antiproliferative activity against broad spectrum of cancer cell lines [4].

The aim of presented work was the synthesis of a series of new N-acylbenzenesulfonamides with potential anticancer activity. New compounds were obtained in the one-step reaction of N-[4-chloro-5-methyl-2-(R¹-methylthio)benzenesulfonyl]cyanamide potassium salts with appropriate carboxylic acids (acetic, propionic, isobutyric, cycloheksylopropionic acids and solution of trans-cinnamic  or benzoic acids in water) at reflux. The structure of compounds was confirmed by IR, ¹H NMR, ¹³C NMR spectroscopy and by elemental and X-ray structure analyses.

Anticancer in vitro screening was performed at the Department of Biotechnology, UG – MUG on three cell lines of breast (MCF-7), colon (HCT-116) and cervix (HeLa) cancer, and at the National Cancer Institute (Bethesda, USA) on panel of 60 cell lines derived from 9 types of human tumors. The prominent compounds N-(4-chloro-5-methyl-2-naphthalen-1-ylmethylthiophenylsulfonyl)acetamide and N-(4-chloro-5-methyl-2-naphthalen-1-ylmethylthiophenylsulfonyl)cinnamamideshowed the highest antiproliferative activity toward MCF-7, HCT-116, HeLa cell lines with IC₅₀ in the range of 6-96 µM.

References:
1. Marquez Ruiz J. F., M., et al. Bioorg. Med. Chem. Lett. 21, 6636 (2011).
2. Luo Y., et al. Bioorg. Med. Chem. 19, 4730 (2011).
3. Huang S., et al. Bioorg. Med. Chem. Lett. 16, 3639 (2006).
4. Brożewicz K., Sławiński J., Monatsh. Chem. 143, 975 (2012).

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

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