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癌症治疗药物中的嘌呤骨架

Purine Scaffold in Agents for Cancer Treatment.

作者信息

Wimmer Zdeněk

机构信息

University of Chemistry and Technology in Prague, Department of Chemistry of Natural Compounds, Technická 5, CZ-16610 Prague 6, Czech Republic.

Institute of Experimental Botany of the Czech Academy of Sciences, Isotope Laboratory, Vídeňská 1083, CZ-14220 Prague 4, Czech Republic.

出版信息

ACS Omega. 2025 Apr 29;10(18):18170-18183. doi: 10.1021/acsomega.5c00340. eCollection 2025 May 13.

Abstract

Cancer represents one of the most important and often fatal threats in the human population. Regarding the natural products, the purine scaffold appears in the purine bases in nucleic acids. Purine and its natural derivatives display a number of pharmacological effects. Previous investigations revealed that different compounds bearing the purine scaffold in their molecules belong to a group of potent agents for cancer treatment. Therefore, this review focuses on summarizing recently designed agents for potential cancer treatment bearing the purine scaffold as the key structural motif in the molecules. The reviewed structures clearly show the advantages and disadvantages of different substituents of the key scaffold that affect the final cytotoxic effects of the studied structures. The structure-activity relationship analysis shows a summary of different but potent compounds mentioned in this review and identifies the compounds receiving priority importance due to their high cytotoxicity and exceptional physicochemical characteristics. The effects of metal coordination, the formation of convenient conjugated molecules, and supramolecular self-assembly resulting in the production of biologically active nanovesicles and other nanoassemblies are also demonstrated. The reviewed original studies clearly showed the possible advantages of (a) metal ion coordination, (b) the formation of conjugates, and (c) designing smart and biocompatible nanoassemblies for biological activity in comparison with the characteristics of the parent compounds. This review is based on the most recent articles published in the last two years, 2023-2024, and it represents work with a highly interdisciplinary nature. Even if these original articles are not too numerous within the given period, the investigations published therein have clearly documented the importance of the purine scaffold in pharmacology and in medicinal and supramolecular chemistry.

摘要

癌症是人类面临的最重要且往往致命的威胁之一。关于天然产物,嘌呤骨架存在于核酸的嘌呤碱基中。嘌呤及其天然衍生物具有多种药理作用。先前的研究表明,分子中带有嘌呤骨架的不同化合物属于一类有效的癌症治疗药物。因此,本综述着重总结了最近设计的以嘌呤骨架作为分子关键结构基序的潜在癌症治疗药物。所综述的结构清楚地显示了关键骨架不同取代基的优缺点,这些取代基会影响所研究结构的最终细胞毒性作用。构效关系分析总结了本综述中提到的不同但有效的化合物,并确定了由于其高细胞毒性和特殊物理化学特性而具有优先重要性的化合物。还展示了金属配位、形成便利的共轭分子以及超分子自组装导致产生生物活性纳米囊泡和其他纳米组装体的作用。所综述的原始研究清楚地表明,与母体化合物的特性相比,(a)金属离子配位、(b)共轭物的形成以及(c)设计智能且生物相容的纳米组装体以实现生物活性可能具有优势。本综述基于2023年至2024年这两年间发表的最新文章,它代表了一项具有高度跨学科性质的工作。即使在给定时期内这些原始文章数量不多,但其中发表的研究清楚地记录了嘌呤骨架在药理学、药物化学和超分子化学中的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdc3/12079222/c3acc2d33f2c/ao5c00340_0001.jpg

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