Design, synthesis and antiproliferative properties of some new 5-substituted-2-iminobenzimidazole derivatives

• New 5-substituted-2,3-dihydro-2-iminobenzimidazoles were synthesized.
• Two compounds showed IC50 in the range – 0.64–2.83 nM against HD-29 cells.
• The IC50 of one the compounds against MDA-MB-231 was 6.2 nM.
• One of the compounds exhibited cytotoxic effect against HeLa and Hep G2-cell.
• All tested compounds revealed proliferative activities to Lep 3 cells.

Some new 1,3,5-substituted-2,3-dihydro-2-imino-benzimidazoles were synthesized under solid–liquid phase transfer catalysis conditions using 5-substituted-2-aminobenzimidazoles as precursors in order to assess their cytotoxicity respectively proliferative activity. The structures of the compounds were confirmed by IR, 1H NMR, 13C NMR and elemental analysis.Compounds 9–10, 12 and 16–17 were evaluated for their cytotoxical effect on four cancer cell lines: HT-29, breast cancer cells MDA-MB-231, HeLa, HepG2 and as well as human diploid cell line Lep-3.Significant cytotoxicity of hydrazone 16 against MDA-MB-231 was established by biologically study, the IC50 was 6.2 nM while the EC50 value to Lep 3 is 0.21 nM. Relative high antiproliferative effects of the acetate 12 and compound 16 against HT-29 were ascertained and the calculated IC50 values were IC50 – 0.85 nM and IC50 – 2.83 nM respectively. Cytotoxic activity against HeLa and HepG2 cells was demonstrated by hydrazone 17, IC50 was 7.2 nM and 117 nM respectively. All tested compounds revealed proliferative activities to human diploid cell line Lep-3. The EC50 values were in the range from 0.05 to 16.91 nM. The obtained results prove the selective cytotoxicity of the tested compounds and are promising for further evaluation of the investigated compounds in vivo experiments using experimentally induced tumors in laboratory animals.

Novel 5-substituted-2,3-dihydro-2-iminobenzimidazoles were synthesized and evaluated for their cytotoxicity. High cytotoxicity was ascertained in test in vitro against HT-29 (IC50 – 0.85 nM resp. 2.83 nM), MDA-MB-231 (IC50 – 6.2), HeLa (IC50 – 117 nM) and HepG2 cancer cells (IC50 – 7.27). A general stimulating effect on the Lep-3 cells was found.Figure optionsDownload as PowerPoint slide