SMC Ecopharm Ltd., Naberezhno-Korchuvatska Street 136-B, Kyiv 03045, Ukraine.
Chemistry Department, National Taras Shevchenko University of Kyiv, Lva Tolstoho Street 12, Kyiv 01033, Ukraine.
Mini Rev Med Chem. 2020;20(2):107-122. doi: 10.2174/1389557519666191009152007.
Quercetin is a plant flavonoid with great potential for the prevention and treatment of disease. Despite the curative application of quercetin is hampered by low bioavailability, its core serves as a scaffold for generating more potent compounds with amplified therapeutic window. This review aims to describe recent advances in the improvement of the pharmacokinetic profile of quercetin via the amino acid prodrug approach which offers wide structural diversity, physicochemical and biological properties improvement. According to the findings, conjugation of quercetin with amino acids results in increased solubility, stability, cellular permeability as well as biological activity. In particular quercetin- amino acid conjugates exhibited potent anticancer, MDR-reversal and antibiotic resistance reversal activities. The synthetic pathways and examples of quercetin-amino acid conjugates are considered. Practical considerations and challenges associated with the development of these prodrugs are also discussed. This mini-review covers the literature on quercetin-amino acid conjugates since 2001 when the first thematic work was published.
槲皮素是一种植物类黄酮，具有很大的疾病预防和治疗潜力。尽管槲皮素的治疗应用受到生物利用度低的阻碍，但它的核心可以作为生成更有效化合物的支架，扩大治疗窗。本综述旨在描述通过氨基酸前药方法改善槲皮素药代动力学特征的最新进展，该方法提供了广泛的结构多样性、物理化学和生物学性质的改善。研究结果表明，槲皮素与氨基酸的结合可提高溶解度、稳定性、细胞通透性以及生物活性。特别是，槲皮素-氨基酸缀合物表现出很强的抗癌、MDR 逆转和抗生素耐药性逆转活性。本文还考虑了槲皮素-氨基酸缀合物的合成途径和实例。还讨论了开发这些前药相关的实际考虑和挑战。本综述涵盖了自 2001 年第一份专题工作发表以来有关槲皮素-氨基酸缀合物的文献。
