Bis-iodine-labeled Curcumin as a Potential CT Imaging Agent for β-amyloid Plaques in the Brain.

IF 2.7 4区医学 Q3 NEUROSCIENCES

CNS & neurological disorders drug targets Pub Date : 2023-01-01 DOI:10.2174/1871527321666220707091435

Yaqian Dai, Liduo Peng, Xiaoyan Tian, Xingwang Wu, Yuanhong Xu, Taoshan Jiang, Jinping Qiao

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引用次数: 1

Abstract

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, K_d 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.

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双碘标记姜黄素作为脑内β-淀粉样斑块的潜在CT显像剂。

背景:阿尔茨海默病(AD)是痴呆症最常见的病因之一，影响着许多老年人。目的:通过设计和合成脑内成像探针，试图为AD的早期诊断提供新的解决方案。方法:设计合成双碘标记姜黄素，并通过体内和体外实验验证其性能。结果:合成了双碘标记的姜黄素(7,BICUR)。在体外质谱结合实验中，BICUR与Aβ1-40和Aβ1-42聚集体的Kd值分别为46.29 nM和64.29 nM。与其他姜黄素衍生物类似，BICUR对AD脑邻近切片的Aβ斑块染色呈阳性。BICUR的Log P值为1.45。在生物分布实验中，尾静脉注射后2分钟，BICUR的初始脑摄取最高(与血药浓度相比为5.87%)，并迅速从小鼠脑中清除。急性毒性实验中，BICUR表现为低毒性，LD50 >100 mg/kg。此外，BICUR在体外具有较高的稳定性(在小鼠脑匀浆中培养120min后，BICUR保持86.68%不变)。此外，BICUR增强了CT成像效果，在体外可敏感检测到，但脑内注射后也与周围组织有明显的分化。结论:所有结果提示BICUR可能作为脑内β斑块的靶向CT显像剂。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

CNS & neurological disorders drug targets 医学-神经科学

CiteScore

5.10

自引率

3.30%

发文量

158

审稿时长

6-12 weeks

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.