Shin, Naewoo Neo Jeon, Hanna Jung, Youngeun Baek, Seungyeop Lee, Sejin Yoo, Hee Chan Bae, Gi Hun Park, Keunwan Yang, Seung-Hoon Han, Jung Min Kim, Ikyon Kim, YoungSoo 2024-01-19T20:01:49Z 2024-01-19T20:01:49Z 2021-09-02 2019-06 1948-7193 https://pubs.kist.re.kr/handle/201004/119946 Recent clinical approvals of brain imaging radiotracers targeting amyloid-beta provided clinicians the tools to detect and confirm Alzheimer's disease pathology without autopsy or biopsy. While current imaging agents are effective in postsymptomatic Alzheimer's patients, there is much room for improvement in earlier diagnosis, hence prompting a need for new and improved amyloid imaging agents. Here we synthesized 41 novel 1,4-naphthoquinone derivatives and initially discovered 14 antiamyloidogenic compounds via in vitro amyloid-beta aggregation assay; however, qualitative analyses of these compounds produced conflicting results and required further investigation. Follow-up docking and biophysical studies revealed that four of these compounds penetrate the blood-brain barrier, directly bind to amyloid-beta aggregates, and enhance fluorescence properties upon interaction. These compounds specifically stain both diffuse and dense-core amyloid-beta plaques in brain sections of APP/PS1 double transgenic Alzheimer's mouse models. Our findings suggest 1,4-naphthoquinones as a new scaffold for amyloid-beta imaging agents for early stage Alzheimer's. English AMER CHEMICAL SOC CYTOTOXIC ACTIVITIES PROTEIN OLIGOMERS CROSS-LINKING BETA PLAQUES DERIVATIVES NAPHTHOQUINONES ANTIBACTERIAL INHIBITION BINDING MODEL Fluorescent 1,4-Naphthoquinones To Visualize Diffuse and Dense-Core Amyloid Plaques in APP/PS1 Transgenic Mouse Brains Article 10.1021/acschemneuro.9b00093 1 ACS CHEMICAL NEUROSCIENCE, v.10, no.6, pp.3031 - 3044 ACS CHEMICAL NEUROSCIENCE 10 6 3031 3044 scie scopus 000472678800042 2-s2.0-85065497388 Biochemistry & Molecular Biology Chemistry, Medicinal Neurosciences Biochemistry & Molecular Biology Pharmacology & Pharmacy Neurosciences & Neurology Article CYTOTOXIC ACTIVITIES PROTEIN OLIGOMERS CROSS-LINKING BETA PLAQUES DERIVATIVES NAPHTHOQUINONES ANTIBACTERIAL INHIBITION BINDING MODEL Alzheimer&apos s disease amyloid diffuse plaques 1,4-naphthoquinone imaging agent A beta