Exploring the pharmaceutical potential of ammonium organotrifluoroborate functional group: Comprehensive chemical, metabolic, and plasma stability evaluation

IF 6 2区医学 Q1 CHEMISTRY, MEDICINAL European Journal of Medicinal Chemistry Pub Date : 2024-09-06 DOI:10.1016/j.ejmech.2024.116844

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Abstract

Boronated carbohydrate derivatives have good potential for targeting malignant cells in Boron Neutron Capture Therapy (BNCT) due to their preferential glucose uptake. In particular, with the introduction of the ammonium trifluoroborate moiety, boronated sugars can function as both BNCT agents and Positron Emission Tomography (PET) tracers. Their ¹⁸F radiolabeling allows real-time tracking of biodistribution. This study evaluates the chemical, metabolic, and plasma stability of ammonium trifluoroborates for pharmaceutical purposes using LC-HRMS, presenting stability data under various conditions -acidic, basic, pseudophysiological, and oxidative- and highlighting degradation products and mechanisms. The data are supported by ¹H NMR and ¹⁹F NMR. Metabolic and plasma stabilities, along with preliminary toxicological data (MTT assays), are also provided to better predict the clinical applicability of these compounds.

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探索有机三氟硼酸铵官能团的制药潜力：化学、代谢和血浆稳定性综合评估

在硼中子俘获疗法（BNCT）中，硼化碳水化合物衍生物因其优先摄取葡萄糖而具有靶向恶性细胞的良好潜力。特别是在引入三氟硼酸铵分子后，硼化糖既可作为硼中子俘获治疗剂，也可作为正电子发射断层扫描（PET）示踪剂。它们的 18F 放射性标记可以实时跟踪生物分布。本研究利用 LC-HRMS 评估了用于制药的三氟硼酸铵的化学、代谢和血浆稳定性，提供了在各种条件（酸性、碱性、假生理和氧化）下的稳定性数据，并重点介绍了降解产物和机制。这些数据得到了 1H NMR 和 19F NMR 的支持。此外，还提供了代谢和血浆稳定性以及初步毒理学数据（MTT 试验），以便更好地预测这些化合物的临床适用性。

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来源期刊

European Journal of Medicinal Chemistry 化学-医药化学

CiteScore

11.70

自引率

9.00%

发文量

863

审稿时长

29 days

期刊介绍： The European Journal of Medicinal Chemistry is a global journal that publishes studies on all aspects of medicinal chemistry. It provides a medium for publication of original papers and also welcomes critical review papers. A typical paper would report on the organic synthesis, characterization and pharmacological evaluation of compounds. Other topics of interest are drug design, QSAR, molecular modeling, drug-receptor interactions, molecular aspects of drug metabolism, prodrug synthesis and drug targeting. The journal expects manuscripts to present the rational for a study, provide insight into the design of compounds or understanding of mechanism, or clarify the targets.