Unravelling the potency of triazole analogues for inhibiting α-synuclein fibrillogenesis and in vitro disaggregation

A series of triazole-based compounds was synthesized using a click chemistry approach and evaluated for the inhibition of alpha-synuclein (alpha-syn) fibrillogenesis and its disaggregation. Compounds Tr3, Tr7, Tr12, Tr15, and Tr16 exhibited good effect in inhibiting alpha-syn fibrillogenesis confirmed by Thioflavin-T assay and fluorescence microscopy and alpha-syn disaggregation confirmed by fluorescence microscopy. Molecular docking was used to understand the plausible mechanism of the test compounds for inhibiting the alpha-syn fibrillogenesis and to verify the in vitro results. Compounds Tr3, Tr7, Tr12, Tr15 and Tr16 showed good binding interactions with the essential amino acid residues of alpha-syn. The compounds which were found to be good inhibitors or disaggregators had no toxic effects on the SH-SY5Y cell line. These compounds have the potential to be developed as therapeutic interventions against synucleinopathies including Parkinson's disease and Lewy body dementia.

Automated summary

A series of triazole-based compounds were synthesized and evaluated for their inhibitory effects on alpha-synuclein fibrillogenesis and disaggregation. The compounds showed good binding interactions with alpha-syn and had no toxic effects on cells, indicating potential as therapeutic interventions for synucleinopathies such as Parkinson's disease and Lewy body dementia.