Synthesis of 2-Pyridyl-benzimidazole Iridium(III), Ruthenium(II), and Platinum(II) Complexes. Study of the Activity as Inhibitors of Amyloid-β Aggregation and Neurotoxicity Evaluation

Abstract

The design of small molecules that can target the aggregation of Aβ as potential therapeutic agents for Alzheimer's disease is an area of study that has attracted a lot of attention recently. The novel ligand methyl 1-butyl-2-pyridyl-benzimidazole carboxylate was prepared for the synthesis of a series of new iridium(III), ruthenium(II), and platinum(II) 2-pyridyl-benzimidazole complexes. The crystal structure of the half-sandwich iridium(III) complex was established by X-ray diffraction. An arrangement of two cationic complexes in the unit cell is observed, and it seems to be organized by weak π···π interactions that are taking place between two symmetry-related benzimidazole ring systems. All new compounds inhibited aggregation of Aβ1-42 in vitro as shown by both thioflavin T fluorescence assay and transmission electron microscopy. Among them the Ir compound rescued the toxicity of Aβ1-42 in primary cortical neurons effectively.

Carbohydrate triazole tethered 2-pyridyl-benzimidazole ligands: Synthesis of their palladium (II) complexes and antimicrobial activities

“…The -CH 2 protons of the propargyl group appeared as a doublet at 5.8 ppm and the phenyl protons appeared as two doublets located at 6.9 ppm and 7.4 ppm. The protons of the benzimidazole appeared as reported in the literature[41]. In the13 C NMR spectrum, the propargyl carbons were observed at 35.3, 72.7 and 78.1 ppm.…”

“…In recent times, the metal-bioconjugate complexes have gained substantial attention [36]. The 2-pyridyl-benzimidazole ligand is capable of coordinating to various metals [37][38][39][40][41][42][43][44] and to form conjugates with biomolecules such as carbohydrates via the N-donor atoms [47].…”

Function and toxicity of amyloid beta and recent therapeutic interventions targeting amyloid beta in Alzheimer's disease

“…110 Further, Engel et al also developed thiophene-based bis(hydroxphenyl)thiophene inhibitors. 112 Recently, an enantioselective triple helical dinuclear metallosupramolecular complex was designed as a first chiral Ab inhibitor. A series of 2-pyridyl-benzimidazole-based Ir(III) (19), Ru(II) and Pt(II) metal complexes were synthesized and demonstrated to rescue primary cortical neuronal cells from Ab toxicity.…”

Organoruthenium Complexes with C^N Ligands are Highly Potent Cytotoxic Agents that Act by a New Mechanism of Action

“…Earlier reports have shown that benzimidazole is a widely used pharmacophore, acting either as anti ‐angiogenic and antitumor agents or amyloid‐β aggregation inhibitors . To obtain new biologically active transition‐metal complexes with improved ability to kill cancer cells and elucidate the mechanism of action of organometallic complexes with C^N ligands along with the optimization of the choice of the transition‐metal moiety and C^N ligands, we designed four kinetically inert ruthenium‐based agents of the type [Ru(C^N)(N^N) 2 ][PF 6 ] (Figure ).…”