Optical Characteristics and Neuroprotective Properties of β-Dimethylaminoethylamide N-Benzoyl-DL-valine Iodmethylate and 1-(β-Diethylaminoethyl)-2-phenyl-4-benzylidene-5-imidazolone

Abstract

The water and DMSO solutions of two new synthesized compounds, β-dimethylaminoethylamidine N-benzoyl-DL-valineiodomethylate (TVA) and 1-(β-diethylaminoethyl)-2-phenyl-4-benzylidene-5-imidazolone (TVS), were characterized by optical absorbance and fluorescence properties. Earlier, the antiacetylcholinesterase and antibutyrylcholinesterase activities of these compounds have been shown. To prove the eligibility of their use against Alzheimer’s disease, the present study demonstrates the ability of the compounds to reduce the aggregation degree of commercial Aβ(1-42) amyloid peptide in vitro. From the concentration dependences, their IC₅₀ values were estimated in the deceleration of Aβ(1-42) aggregation (1.56 ± 0.3 mM for TVA and 1.8 ± 0.28 mM for TVS). The effective destabilization of the preformed aggregates of the peptide was registered with the IC₅₀ values of 0.54 ± 0.06 and 0.67 ± 0.2 mM, for TVA and TVS, respectively. Cell culture experiments have shown the effectiveness of the synthesized compounds in protection the rat hippocampal cells against cytotoxic action of Aβ(1-42) aggregates: during 7 days incubation, the number of neurospheres per microscopic field in the presence of the peptide aggregates fallen down to 34% of the intact cells, but 2 μg/mL TVA kept the cells on the level of the intact, and 5 μg/mL TVS—on the level of 77% of the intact. Subsequent developments based on these compounds will allow the researchers to create the preparations valid for pre-clinical studies with goal to introduce into medical practice as new remedies in prevention/treatment of Alzheimer’s disease.