期刊
CHEMISTRY & BIODIVERSITY
卷 -, 期 -, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbdv.202301113
关键词
aminobenzothiazole; Amyloid beta (A beta); molecular dynamic simulation (MD); pro-aggregator; root mean square deviation (RMSD)
Novel inhibitors based on benzo[d]thiazol-2-yl)-1phenylmethanimine derivatives were designed to reduce aggregation in Alzheimer’s disease. The biological evaluation showed compound 5a and 7e as the most effective inhibitors of Aβ aggregation.
Some novel inhibitors based on the (benzo[d]thiazol-2-yl)-1phenylmethanimine derivatives were designed to reduce the aggregation process in Alzheimer's disease. These structures seem to mimic stilbene-like scaffold, while the benzothiazole moiety locks the thioflavin T binding site. Other inhibitors were designed based on 2-((benzo[d]thiazol-2-ylimino)methyl)5-(benzyloxy)-1-methylpyridin-4(H)-one derivatives. Benzo[d]thiazol-2-amine derivatives were prepared by the reaction of aniline derivatives with ammonium thiocyanate in the presence of bromine/acetic acid. Then, the reaction of amines with benzaldehyde derivatives and 5-(benzyloxy)-1methyl-4-oxo-1,4-dihydropyridine-2-carbaldehyde gave the desired compounds. The plate reader-based fibrillation assay was done to evaluate the inhibition of A ss aggregation. Also, molecular dynamic simulation was carried out to clarify the interaction manner of the designed compounds with A ss formation. The biological evaluation proved 5a and 7e as the best inhibitor of the A ss aggregation. compound 5a in the concentration of 50 mu M inhibited A ss fibril formation better than 7e. MD simulation elucidated that the A ss aggregation inhibitors in different concentrations represented different binding conformations throughout the entire or in one area of A ss. MD showed the ligands in lower concentrations accumulate in an area of A ss aggregations and separate one fibril from the aggregated A ss. On the contrary, in higher concentrations, the ligands tend to be located through the entire A ss.
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