Unravelling the potency of triazole analogues for inhibiting α-synuclein fibrillogenesis andin vitrodisaggregation
- 22 January 2021
- journal article
- research article
- Published by Royal Society of Chemistry (RSC) in Organic & Biomolecular Chemistry
- Vol. 19 (7), 1589-1603
- https://doi.org/10.1039/d0ob02226h
Abstract
A series of triazole-based compounds was synthesized using a click chemistry approach and evaluated for the inhibition of α-synuclein (α-syn) fibrillogenesis and its disaggregation. Compounds Tr3, Tr7, Tr12, Tr15, and Tr16 exhibited good effect in inhibiting α-syn fibrillogenesis confirmed by Thioflavin-T assay and fluorescence microscopy and α-syn disaggregation confirmed by fluorescence microscopy. Molecular docking was used to understand the plausible mechanism of the test compounds for inhibiting the α-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 α-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.Funding Information
- Council of Scientific and Industrial Research, India (09/466(0182)2K17 EMR-I)
- Department of Biotechnology, Ministry of Science and Technology, India (SAA315992363)
- University Grants Commission (201516-RGNF-2015-17-SC-UTT-4463)
- Ministry of Human Resource Development
- Science and Engineering Research Board (CRG/2018/004960)
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