Modified tetrahalogenated benzimidazoles with CK2 inhibitory activity are active against human prostate cancer cells LNCaP in vitro.

Abstract

A series of novel CK2 inhibitors, tetrahalogenated benzimidazoles carrying an aminoalkylamino group at position 2, has been prepared by nucleophilic substitution of the respective 2,4,5,6,7-pentabromobenzimidazoles and 2-bromo-4,5,6,7-tetraiodobenzimidazoles. The new derivatives as well as some previously obtained tetrahalogenobenzimidazoles, including 4,5,6,7-tetrabromobenzimidazole (TBI) and 4,5,6,7-tetraiodobenzimidazole (TIBI), were evaluated for activity against the hormone-sensitive human prostate cancer cell line LNCaP. The activity of 2-aminoalkylamino derivatives was notably higher (LD(50) 4.75-9.37 μM) than that of TBI and TIBI (LD(50) ≈ 20 μM). The determination of the LD(50) value identified the 2-aminoethylamino-4,5,6,7-tetraiodobenzimidazole with an additional methyl group at position 1 (6) as the most efficient compound (LD(50): 4.75 ± 1.02 μM). Interestingly, there was no clear correlation between cell viability and apoptosis induction indicating additional cell death mechanisms.

• Authors: Carolin C Schneider, Sabine Kartarius, Mathias Montenarh, Andrzej Orzeszko, Zygmunt Kazimierczuk
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 20 Issue 14 Pg. 4390-6 (Jul 15 2012) ISSN: 1464-3391 [Electronic] England
• PMID: 22698781 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Benzimidazoles
• Protein Kinase Inhibitors
• Casein Kinase II

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, toxicity)
• Apoptosis (drug effects)
• Benzimidazoles (chemical synthesis, chemistry, toxicity)
• Casein Kinase II (antagonists & inhibitors, metabolism)
• Cell Line, Tumor
• Humans
• Male
• Prostatic Neoplasms
• Protein Kinase Inhibitors (chemical synthesis, chemistry, toxicity)