Synthesis, characterization and cytotoxicity of some novel 1,3-disubstituted-2,3-dihydro-2-iminobenzimidazoles

Some new 1,3-disubstituted-2,3-dihydro-2-iminobenzimidazoles were synthesized using 1-(un)substituted-2-aminobenzimidazoles as precursors in order to determine their cytotoxicity. The structures of the compounds were confirmed by IR, 1H NMR, 13C NMR and elemental analysis.Compounds 4, 7–11 and 13–14 were evaluated for their cytotoxical effect on two cancer cell lines: human colorectal cancer cell line HT-29, breast cancer cells MDA-MB-231 and as well as normal spleen cells. The distinctly marked antiproliferative activity of 1,3-bis(3-phenylpropyl-1)-1,3-dihydro-2H-benzimidazol-2-imine hydro bromide 7, N-(aminopropyl)-2-(3-{2-[(aminopropyl)-amino]-2-oxoethyl}-2-imino-2,3-dihydro-1H-benzimidazol-1-yl)acetamide 9 and 1,3-bis[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-2,3-dihydro-2H-benzimidazol-2-imine 11 against human colorectal cancer cell line HT-29 was ascertained and the calculated IC50 were 9.26, 0.56 and 0.013 nM respectively. Compounds 4, 9, 10 and 13 exhibited relative high cytotoxic activity against MDA-MB-231 cells. The calculated IC50 values were in the range 0.123–1.65 nM. All tested compounds excluding compound 1,3-bis[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-2,3-dihydro-2H-benzimidazol-2-imine (11) revealed proliferative activities to normal spleen cells. The computed EC50 values varied from 0.05 to 16.91 nM.

Graphical abstractNovel derivatives of 2,3-dihydro-2-iminobenzimidazoles were synthesized and evaluated for their cytotoxicity. High cytotoxicity was ascertained in test in vitro against HT-29, MDA-MB-231 cells and a general stimulating effect on normal spleen cells.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Optimized synthesis of new 1,3-disubstituted-2,3-dihydro-2-iminobenzimidazoles. ► MTS–test was used to establish the cytotoxicity of the tested compounds. ► Three of the compounds showed IC50 in the range 9.26–0.013 nM against HD-29 cells. ► Some of the compounds exhibited cytotoxical effect against MDA-MB-231 cells. ► Most of the compounds revealed proliferative activities to normal spleen cells.