n -氧化物肉桂苯胺衍生物PX5-9的设计和表征：改善溶解度和上调BDNF

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Bioorganic & Medicinal Chemistry Letters Pub Date : 2025-05-22 DOI:10.1016/j.bmcl.2025.130266

Zhixian Zhang , Qianhui Shen , Yanping Chen , Zhi Liang , Yuan Liu , Yu Ren , Cailv Wei , Kang Jia , Chao Ding , Shisong Wang , Rongbiao Pi

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引用次数: 0

摘要

化合物5，肉桂苯胺衍生物，上调脑衍生神经营养因子（BDNF）的表达，但具有低溶解性。在本研究中，5的n -氧化物衍生物PX5-9在HT22谷氨酸诱导的毒性模型中显示出明显的保护作用，在30 μM下无明显毒性。Western blot分析证实PX5-9增加BDNF水平与5相似。溶解度测试显示PX5-9与5 (<；15 ng / mL)。PX5-9的药代动力学研究显示其具有良好的特性，吸收快，并且可以转化为母体化合物5，提示其是BDNF相关疾病的潜在候选者。n -氧化物修饰可能是一个很好的前药设计，以提高溶解度，同时保持生物活性。

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Design and characterization of N-oxide cinnamanilide derivative PX5–9: Improved solubility and BDNF upregulation

Compound 5, a cinnamanilide derivative, upregulates brain derivated neurotrophic factor (BDNF) expression but with low soluablity. In this study, PX5–9, a N-oxide derivative of 5, demonstrated significant protective effects in the HT22 glutamate-induced toxicity model and showed no significant toxicity at 30 μM. Western blot analysis confirmed that PX5–9 increased BDNF levels similar to 5. Solubility tests revealed a significant improvement in PX5–9 (37.10 ± 0.33 μg/mL) compared to 5 (< 15 ng/mL). Pharmacokinetic studies of PX5–9 revealed favorable properties, fast absorption and also can be transformated into parent compound 5, suggesting it is a potential candidate for these diseases involving with BDNF. The N-oxide modification might be a good prodrug design to enhance solubility while preserving biological activity.

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来源期刊

Bioorganic & Medicinal Chemistry Letters 医学-医药化学

CiteScore

5.70

自引率

3.70%

发文量

463

审稿时长

27 days

期刊介绍： Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.