叶酸共轭有机 CO 原药:合成和二氧化碳释放动力学研究

IF 2.6 4区 医学 Q3 CHEMISTRY, MEDICINAL
Shameer M. Kondengadan, Shubham Bansal, Xiaoxiao Yang, Binghe Wang
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引用次数: 0

摘要

一氧化碳(CO)是一种内源性分子,在炎症、器官损伤、结肠炎和癌症转移的动物模型中显示出疗效。由于一氧化碳具有气态性质,因此需要开发高效的一氧化碳递送方法,尤其是能够靶向递送的方法。在本研究中,我们旨在利用之前报道的富集触发原药活化方法,通过靶向叶酸受体实现靶向递送。总体思路是利用叶酸受体介导的富集作用来加速双分子 Diels-Alder 反应,从而实现原药活化。在此过程中,我们首先需要找到调整反应动力学的方法,以确保在没有富集的情况下反应最小,而在富集后活化最佳。在这项可行性研究中,我们合成了两对二烯双亲化合物,并研究了它们的反应动力学和靶向叶酸受体的能力。我们发现,叶酸共轭会显著影响原始二烯双亲化合物对的反应动力学。这些信息对于今后设计类似的二氧化碳靶向递送方法非常有用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Folate-conjugated organic CO prodrugs: Synthesis and CO release kinetic studies

Folate-conjugated organic CO prodrugs: Synthesis and CO release kinetic studies

Carbon monoxide (CO) is an endogenously produced molecule and has shown efficacy in animal models of inflammation, organ injury, colitis and cancer metastasis. Because of its gaseous nature, there is a need for developing efficient CO delivery approaches, especially those capable of targeted delivery. In this study, we aim to take advantage of a previously reported approach of enrichment-triggered prodrug activation to achieve targeted delivery by targeting the folate receptor. The general idea is to exploit folate receptor-mediated enrichment as a way to accelerate a bimolecular Diels-Alder reaction for prodrug activation. In doing so, we first need to find ways to tune the reaction kinetics in order to ensure minimal reaction without enrichment and optimal activation upon enrichment. In this feasibility study, we synthesized two diene-dienophile pairs and studied their reaction kinetics and ability to target the folate receptor. We found that folate conjugation significantly affects the reaction kinetics of the original diene-dienophile pairs. Such information will be very useful in future designs of similar targeted approaches of CO delivery.

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来源期刊
Medicinal Chemistry Research
Medicinal Chemistry Research 医学-医药化学
CiteScore
4.70
自引率
3.80%
发文量
162
审稿时长
5.0 months
期刊介绍: Medicinal Chemistry Research (MCRE) publishes papers on a wide range of topics, favoring research with significant, new, and up-to-date information. Although the journal has a demanding peer review process, MCRE still boasts rapid publication, due in part, to the length of the submissions. The journal publishes significant research on various topics, many of which emphasize the structure-activity relationships of molecular biology.
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