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This study explores the potential of a series of novel compounds as candidates for the treatment of Alzheimer's Disease. Compound 6i shows promising activity in increasing cell viabilities and inhibiting AChE. It also has a higher potential against Aβ1-42 aggregation compared to compound 6e. Compound 6i presents a promising multi-targeted profile for treating Alzheimer's Disease.
In this study, combining the thiazole and cinnamoyl groups into the styryl-thiazole scaffold, a series of novel styryl-thiazole hybrids (6a-p) was rationally designed, synthesized, and evaluated by the multi-target-directed ligands strategy as potential candidates for the treatment of Alzheimer’s Disease (AD). Hybrids 6e and 6i were the most promising among the synthesized hybrids since they were able to significantly increase cell viabilities in Aβ1-42-exposed-human neuroblastoma cell line (6i at the concentration of 50 µg/mL and 6e at the concentration of 25 µg/mL resulted in ~34% and ~30% increase in cell viabilities, respectively). Compounds 6e and 6i exhibited highly AChE inhibitory properties in the experimental AD model at 375.6 ± 18.425 mU/mL and 397.6 ± 32.152 mU/mL, respectively. Moreover, these data were also confirmed by docking studies. Compared to hybrid 6e and according to the results, 6i also has the highest potential against Aβ1-42 aggregation with over 80% preventive activity. The in-silico prediction of the physicochemical properties of hybrids confirmed that 6i possesses a better profile compared to 6e. Therefore, compound 6i presented a promising multi-targeted active molecular profile for treating AD considering the multifactorial nature of AD, and it is reasonable to deepen its mechanisms of action in an in vivo experimental model of AD.
This article is Open Access
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