Recently, we reported on the significant anticancer activity of a series of 2-mercapto-N-(1,2,4-triazin-3-yl)benzenesulfonamides bearing phenyl or substituted phenyl attached to the 1,2,4-triazine moiety simultaneously at positions 5 and 6 [1]. In the present study, in search for even more potent 2-mercaptobenzenesulfonamides we elaborated the synthesis and anticancer evaluations in vitro of novel N-(5-substituted 1,2,4-triazin-3-yl)benzenesulfonamide derivatives as depicted in scheme below.
The synthesis of the desired 2-benzylthio-4-chloro-N-(5-aryl-1,2,4-triazin-3-yl)benzenesulfonamide derivatives were  achieved by reacting of the corresponding 3-amino-2-(benzenesulfonyl)guanidines [2,3] with suitable phenylglyoxal hydrate in refluxing glacial acetic acid for at least 30 hours. The structure of the obtained compounds was confirmed by elemental analyses, and IR, ¹H and ¹³C NMR spectroscopy.

Anticancer in vitro screening was performed at the Department of Biotechnology, Intercollegiate Faculty of Biotechnology UG-MUG with using three cell lines of breast (MCF-7), colon (HCT-116) and cervix cancer (HeLa), and at the NCI (Bethesda MD, USA) using 60 cell lines derived from 9 types of human tumors. This tests revealed moderate or reasonable anticancer activity of tested compounds.
The distinctive compound, i.e. 2-benzylthio-4-chloro-N-[5-(3-methoxyphenyl)-1,2,4-triazin-3-yl]-5-methylbenzenesulfonamide showed remarkable activity against 23 of human tumor cell lines representing leukemia, lung, colon, CNS, melanoma, ovarian, renal and breast at low micromolar GI₅₀ level in the range of 13.8 – 19.9 μM.

References:
1. Sławiński J., Gdaniec M., Eur. J. Med. Chem., 40, 377 (2005).
2. Sławiński J., Polish J. Chem., 75, 1309 (2001).
3. Sławiński J., Bednarski P., Grünert R., Reszka P., Polish J. Chem., 77, 53 (2003).

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

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