biostudies-literatureElbatrawy AABoston UniversityEdward Lowe FoundationNIA NIH HHSMichigan State UniversityNINDS NIH HHSRobert J. Kleberg, Jr. and Helen C. Kleberg FoundationNIHAlzheimer's AssociationLowe Foundation117990https://www.ebi.ac.uk/biostudies/studies/S-EPMC11645236biostudies-literatureUnknown116Tau and α-synuclein (α-syn) are prone-to-aggregate proteins that can be responsible for pathological lesions found in the brains of Alzheimer's disease (AD), Lewy body dementia (LBD), and Parkinson's disease (PD) patients. The early-stage oligomers and protofibrils of tau are believed to be strongly linked to human cognitive impairment while the toxic α-syn oligomers are associated with behavioral motor deficits. Therefore, concurrent targeting of both proteinaceous aggregates and oligomers are very challenging. Herein, rhodanine-based compounds were designed and synthesized to target the fibrils and oligomers of tau and α-syn proteins. In particular, the indole-containing rhodanines 5l and 5r displayed significantly high anti-aggregation activity towards α-syn fibrils by reducing of the tBioorganic & medicinal chemistryExploring the rhodanine universe: Design and synthesis of fluorescent rhodanine-based derivatives as anti-fibrillar and anti-oligomer agents against α-synuclein and 2N4R tau.PMC11645236R21 NS121826K08 AG071985NS121826R01 NS099328NS099328AARFD-17-5297421N4RAG071985Elbatrawy AAAlnakhala HFortin JSPerry GDettmer UZhu XTripathi APlascencia-Villa GAdemoye TAfalseExploring the rhodanine universe: Design and synthesis of fluorescent rhodanine-based derivatives as anti-fibrillar and anti-oligomer agents against α-synuclein and 2N4R tau.Tau and α-synuclein (α-syn) are prone-to-aggregate proteins that can be responsible for pathological lesions found in the brains of Alzheimer's disease (AD), Lewy body dementia (LBD), and Parkinson's disease (PD) patients. The early-stage oligomers and protofibrils of tau are believed to be strongly linked to human cognitive impairment while the toxic α-syn oligomers are associated with behavioral motor deficits. Therefore, concurrent targeting of both proteinaceous aggregates and oligomers are very challenging. Herein, rhodanine-based compounds were designed and synthesized to target the fibrils and oligomers of tau and α-syn proteins. In particular, the indole-containing rhodanines 5l and 5r displayed significantly high anti-aggregation activity towards α-syn fibrils by reducing of the t2024-01-01T00:00:00Z2024 Dec2025-04-04T09:13:01.038Z2025-04-04T09:13:01.038ZS-EPMC116452363955089110.1016/j.bmc.2024.117990