Synthesis of 3-(2-Alkylthio-4-chloro-5-methylbenzenesulfonyl)-2-(1-phenyl-3-arylprop-2-enylideneamino)guanidine Derivatives with Pro-Apoptotic Activity against Cancer Cells

The untypical course of reaction between chalcones and benzenesulfonylaminoguanidines led to the new 3-(2-alkylthio-4-chloro-5-methylbenzenesulfonyl)-2-(1-phenyl-3-arylprop-2-enylideneamino)guanidine derivatives 8-33. The new compounds were tested in vitro for their impact on the growth of breast cancer cells MCF-7, cervical cancer cells HeLa and colon cancer cells HCT-116 by MTT assay. The results revealed that the activity of derivatives is strongly related to the presence of hydroxy group in the benzene ring at the 3-arylpropylidene fragment. The most cytotoxic compounds 20 and 24 displayed mean IC50 values of 12.8 and 12.7 mu M, respectively, against three tested cell lines and were almost 3- and 4-fold more active toward MCF-7 and HCT-116 when compared with non-malignant HaCaT cells. Furthermore, compound 24 induced apoptosis in cancer cells and caused a decrease of mitochondrial membrane potential as well as an increase of cells in sub-G1 phase in contrast to its inactive analog 31. The strongest activity against the most sensitive HCT-116 cell line was found for compound 30 (IC50 = 8 mu M), which was 11-fold more effective in the growth inhibition of HCT-116 cells than those of HaCaT cells. Based on this fact, the new derivatives may be promising leading structures for the search for agents for the treatment of colon cancer.

Automated summary

The reaction between chalcones and benzenesulfonylaminoguanidines resulted in the synthesis of new guanidine derivatives. These compounds were tested for their impact on the growth of breast cancer cells MCF-7, cervical cancer cells HeLa, and colon cancer cells HCT-116. The presence of a hydroxy group in the benzene ring was found to strongly affect the activity of the derivatives. The most cytotoxic compounds displayed significant inhibitory effects on the tested cell lines, particularly against the malignant cells.