Abstract
ligand.We next performed an in situ competitive binding assay to determine their selective binding affinity for CAA over neuritic plaques in brain tissues of aged Tg2576 mice having both CAA deposits and neuritic plaques. The lipophilicity of phenoxazine derivatives was determined by octanol-water coefficient to predict their brain accessibility. Results: We found that phenoxazine derivatives, in particular 5-5, revealed enhanced binding affinity for CAA as compared with the parental compound. More importantly, synthesized phenoxazine analogs preserved the preferential binding affinity for CAA over neuritic plaques. Conclusions: These results strongly suggest that phenoxazine analogs provide great potential for development of a CAA-specific amyloid tracer that would be a major diagnostic step forward for this frequent (but often under-diagnosed) condition.
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