Novel Furan-2-yl-1H-pyrazoles Possess Inhibitory Activity against α-Synuclein Aggregation

• DOI: 10.1021/acschemneuro.0c00252
• Publication Date: 2020-06-18T13:11:33Z
• Authors: Philip Ryan; Mingming Xu; Kousar Jahan; Andrew K. Davey; Prasad V. Bharatam; Shailendra Anoopk...; Michael Kassiou; George D. Mellick; Santosh Rudrawar
• Keywords: 0303 health sciences; 610; Parkinson Disease; 540; 3. Good health; Structure-Activity Relationship; 03 medical and health sciences; Biochemistry and cell biology; Medicinal and biomolecular chemistry; alpha-Synuclein; Humans; Pyrazoles; Furans; Analytical chemistry

A series of novel furan-2-yl-1H-pyrazoles and their chemical precursors were synthesized and evaluated for their effectiveness at disrupting α-synuclein (α-syn) aggregation in vitro. The compounds were found to inhibit α-syn aggregation with efficacy comparable to the promising drug candidate anle138b. The results of this study indicate that compounds 8b, 8l, and 9f may qualify as secondary leads for the structure-activity relationship studies aimed to identify the suitable compounds for improving the modulatory activity targeted at α-syn self-assembly related to Parkinson's disease.