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

Abstract

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, (1)H NMR, (13)C 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 IC(50) 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 IC(50) 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 EC(50) values varied from 0.05 to 16.91 nM.

• Authors: Anelia Ts Mavrova, Diana Wesselinova, Nikolay Vassilev, Jordan A Tsenov
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 46 Issue 8 Pg. 3362-7 (Aug 2011) ISSN: 1768-3254 [Electronic] France
• PMID: 21605925 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Benzimidazoles
• Imines

Topics

• Antineoplastic Agents (chemical synthesis, pharmacology)
• Benzimidazoles (chemical synthesis, pharmacology)
• Breast Neoplasms (drug therapy, pathology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Colorectal Neoplasms (drug therapy, pathology)
• Drug Screening Assays, Antitumor
• Female
• Humans
• Imines (chemical synthesis, pharmacology)
• Inhibitory Concentration 50
• Magnetic Resonance Spectroscopy
• Monocytes (cytology, drug effects)