Scientific reports of recent years indicate that sulfonamide derivatives show in vitro and in vivo antitumor activity with various mechanisms of action, including carbonic anhydrase inhibition, cell cycle perturbation in G1 phase, inhibition of tubulin polymerization or angiogenesis inhibition (inhibition of extracellular matrix metalloproteinases). Natural products containing the cinnamon group attract a lot of attention due to their broad spectrum of biological activity and low toxicity. Thus designing of molecular hybrids, containing in their structure pharmacophore fragments of cinnamic acid and sulfonamide, may lead to compounds with increased biological activity as a result of synergistic effect of both fragments.
The new original 2-(2-arylmethylthio-4-chloro-5-methylbenzenesulfonyl)-1-phenylguanidine derivatives were molecular hybrids containing the pharmacophore core of 4-chloro-2-mercapto-5-methylbenzenesulfonamide and 4-acetylphenyl moiety or chalcone fragment. The designed compounds were obtained by organic synthesis. The structures of the compounds were confirmed by elemental analysis, spectroscopy (IR, 1H NMR, 13C NMR), X-Ray and mass spectrometry.
The obtained compounds were evaluated for their cytotoxic activity in the MTT test against three human tumor cell lines: breast cancer (MCF-7), colon cancer (HCT-116) and cervical cancer (HeLa). It has been shown that a number of 1-(4-acetylphenyl)-2-(benzenesulfonyl)guanidines (series 1) and
2-(benzenesulfonyl)-1-(4-cinnamoylphenyl)guanidines (series 2) are highly active against all cancer cell lines (IC50: 10‒21 μM, series one and 4.7‒15 μM, series two). Additionally, in tests carried out on non-cancer human keratinocyte cell line (HaCaT), it was proved that the tested compounds were selective for cancer cells.
