虫草素衍生物增强生物活性和稳定性的分子工程研究。

IF 3.6 4区医学 Q2 CHEMISTRY, MEDICINAL

ChemMedChem Pub Date : 2025-02-05 DOI:10.1002/cmdc.202400979

Yiming Gu, Wei Yu, Xiang Li, Yingjie Fan, Yanan Liu, Jumreang Tummatorn, Siyu Jiang, Jingyue Yang

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引用次数: 0

摘要

为了解决虫草素在腺苷脱氨酶（ADA）诱导下的代谢不稳定性，并提高其生物活性，本研究利用分子工程技术开发了十一种新型虫草素衍生物。通过加入立体受阻的保护基团和修饰糖基，该研究旨在提高稳定性和功效。抗菌测试表明，与虫草素相比，五种衍生物对致病菌株的活性明显更强，与益生菌的兼容性更好。化合物 2c 对 K562 和 MGC-803 细胞表现出中等程度的抗肿瘤活性，IC50 值分别为 42.21 μM 和 27.79 μM。此外，化合物 4b 还具有显著的 DPPH 自由基清除能力。这些化合物在 ADA 溶液中的稳定性也有所提高，为了解虫草素衍生物的结构-活性关系提供了宝贵的见解。

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Molecular Engineering of Cordycepin Derivatives for Enhanced Biological Activity and Stability.

To address the metabolic instability of cordycepin induced by adenosine deaminase (ADA) and to enhance its bioactivity, this study developed eleven novel cordycepin derivatives using molecular engineering techniques. By incorporating sterically hindered protective groups and modifying the glycosyl moiety, the research aimed to improve both stability and efficacy. Antibacterial tests revealed that five derivatives showed significantly greater activity against pathogenic strains compared to cordycepin, with better compatibility with probiotics. Compound 2 c demonstrated moderate antitumor activity against K562 and MGC-803 cells, with IC₅₀ values of 42.21 μM and 27.79 μM, respectively. Additionally, compound 4 b demonstrated notable DPPH free radical scavenging ability. These compounds also showed improved stability in ADA solutions, providing valuable insights into the structure-activity relationships of cordycepin derivatives.

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来源期刊

ChemMedChem 医学-药学

CiteScore

6.70

自引率

2.90%

发文量

280

审稿时长

1 months

期刊介绍： Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.