{"title":"双碘标记姜黄素作为脑内β-淀粉样斑块的潜在CT显像剂。","authors":"Yaqian Dai, Liduo Peng, Xiaoyan Tian, Xingwang Wu, Yuanhong Xu, Taoshan Jiang, Jinping Qiao","doi":"10.2174/1871527321666220707091435","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is one of the most common causes of dementia, affecting many old people.</p><p><strong>Objectives: </strong>By designing and synthesizing intracerebral imaging probes, we tried to provide a new solution for the early diagnosis of AD.</p><p><strong>Methods: </strong>We designed and synthesized bis-iodine-labeled curcumin, and verified its performance through in vivo and in vitro experiments.</p><p><strong>Results: </strong>In this study, bis-iodine-labeled curcumin (7, BICUR) was synthesized. In the in vitro mass spectrum binding assay, K<sub>d</sub> values of BICUR with Aβ1-40 and Aβ1-42 aggregates were 46.29 nM and 64.29 nM, respectively. Aβ plaques in AD brain adjacent sections were positively stained by BICUR, which was similar to some other curcumin derivatives. The Log P value of BICUR was 1.45. In the biodistribution experiment, BICUR showed the highest initial brain uptake (5.87% compared to the blood concentration) two minutes after the tail vein injection and rapid clearance from the mouse brain. In the acute toxicity experiment, BICUR showed low toxicity, and the LD<sub>50</sub> was >100 mg/kg. Moreover, BICUR showed a high stability in vitro (86.68% unchanged BICUR after incubation for 120min in mouse brain homogenate). Besides, BICUR produced an enhanced CT imaging effect that could be sensitively detected in vitro, but it also showed an obvious differentiation from surrounding tissues after intracerebral injection.</p><p><strong>Conclusion: </strong>All results suggested that BICUR could probably act as a targeted CT imaging agent for Aβ plaques in the brain.</p>","PeriodicalId":10456,"journal":{"name":"CNS & neurological disorders drug targets","volume":"22 7","pages":"1120-1132"},"PeriodicalIF":2.7000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Bis-iodine-labeled Curcumin as a Potential CT Imaging Agent for β-amyloid Plaques in the Brain.\",\"authors\":\"Yaqian Dai, Liduo Peng, Xiaoyan Tian, Xingwang Wu, Yuanhong Xu, Taoshan Jiang, Jinping Qiao\",\"doi\":\"10.2174/1871527321666220707091435\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Alzheimer's disease (AD) is one of the most common causes of dementia, affecting many old people.</p><p><strong>Objectives: </strong>By designing and synthesizing intracerebral imaging probes, we tried to provide a new solution for the early diagnosis of AD.</p><p><strong>Methods: </strong>We designed and synthesized bis-iodine-labeled curcumin, and verified its performance through in vivo and in vitro experiments.</p><p><strong>Results: </strong>In this study, bis-iodine-labeled curcumin (7, BICUR) was synthesized. In the in vitro mass spectrum binding assay, K<sub>d</sub> values of BICUR with Aβ1-40 and Aβ1-42 aggregates were 46.29 nM and 64.29 nM, respectively. Aβ plaques in AD brain adjacent sections were positively stained by BICUR, which was similar to some other curcumin derivatives. The Log P value of BICUR was 1.45. In the biodistribution experiment, BICUR showed the highest initial brain uptake (5.87% compared to the blood concentration) two minutes after the tail vein injection and rapid clearance from the mouse brain. In the acute toxicity experiment, BICUR showed low toxicity, and the LD<sub>50</sub> was >100 mg/kg. Moreover, BICUR showed a high stability in vitro (86.68% unchanged BICUR after incubation for 120min in mouse brain homogenate). Besides, BICUR produced an enhanced CT imaging effect that could be sensitively detected in vitro, but it also showed an obvious differentiation from surrounding tissues after intracerebral injection.</p><p><strong>Conclusion: </strong>All results suggested that BICUR could probably act as a targeted CT imaging agent for Aβ plaques in the brain.</p>\",\"PeriodicalId\":10456,\"journal\":{\"name\":\"CNS & neurological disorders drug targets\",\"volume\":\"22 7\",\"pages\":\"1120-1132\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"CNS & neurological disorders drug targets\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/1871527321666220707091435\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"CNS & neurological disorders drug targets","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/1871527321666220707091435","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Bis-iodine-labeled Curcumin as a Potential CT Imaging Agent for β-amyloid Plaques in the Brain.
Background: Alzheimer's disease (AD) is one of the most common causes of dementia, affecting many old people.
Objectives: By designing and synthesizing intracerebral imaging probes, we tried to provide a new solution for the early diagnosis of AD.
Methods: We designed and synthesized bis-iodine-labeled curcumin, and verified its performance through in vivo and in vitro experiments.
Results: In this study, bis-iodine-labeled curcumin (7, BICUR) was synthesized. In the in vitro mass spectrum binding assay, Kd values of BICUR with Aβ1-40 and Aβ1-42 aggregates were 46.29 nM and 64.29 nM, respectively. Aβ plaques in AD brain adjacent sections were positively stained by BICUR, which was similar to some other curcumin derivatives. The Log P value of BICUR was 1.45. In the biodistribution experiment, BICUR showed the highest initial brain uptake (5.87% compared to the blood concentration) two minutes after the tail vein injection and rapid clearance from the mouse brain. In the acute toxicity experiment, BICUR showed low toxicity, and the LD50 was >100 mg/kg. Moreover, BICUR showed a high stability in vitro (86.68% unchanged BICUR after incubation for 120min in mouse brain homogenate). Besides, BICUR produced an enhanced CT imaging effect that could be sensitively detected in vitro, but it also showed an obvious differentiation from surrounding tissues after intracerebral injection.
Conclusion: All results suggested that BICUR could probably act as a targeted CT imaging agent for Aβ plaques in the brain.
期刊介绍：
Aims & Scope
CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes.
CNS & Neurological Disorders - Drug Targets publishes guest edited thematic issues written by leaders in the field covering a range of current topics of CNS & neurological drug targets. The journal also accepts for publication original research articles, letters, reviews and drug clinical trial studies.
As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal is essential reading for all pharmaceutical scientists involved in drug discovery and development.
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