Structural characterization, cytotoxic and enzyme inhibitory profile of a novel triazole-linked ferrocene hybrid of 18β-glycyrrhetinic acid

IF 2.4 3区化学 Q2 CHEMISTRY, INORGANIC & NUCLEAR

Polyhedron Pub Date : 2025-06-04 DOI:10.1016/j.poly.2025.117620

Zehra Öztürk , Yaren Yıldız , Nurgül Abul , Onur Ertik , Ferda Arı , İlhami Gülçin , Ömer Koz , Gamze Koz

{"title":"Structural characterization, cytotoxic and enzyme inhibitory profile of a novel triazole-linked ferrocene hybrid of 18β-glycyrrhetinic acid","authors":"Zehra Öztürk , Yaren Yıldız , Nurgül Abul , Onur Ertik , Ferda Arı , İlhami Gülçin , Ömer Koz , Gamze Koz","doi":"10.1016/j.poly.2025.117620","DOIUrl":null,"url":null,"abstract":"<div><div>18β-Glycyrrhetinic acid (GA) is a pentacyclic triterpene which was obtained from the roots of Glycyrrhiza glabra known for its diverse pharmaceutical applications. The primary aim of this study is to enhance the pharmaceutical properties of GA by modifying it with a 1,2,3-triazole-functionalized ferrocene moiety. The hybrid compound 3 was synthesized by amide functionalization of GA at the C-30 position with ferrocene, linked via a 1,4-disubstituted 1,2,3-triazole bridge. Additionally, the C-3 hydroxyl group of GA was converted into an acetyl ester. The hybrid compound 3 was characterized using FT-IR, NMR (1H and 13C) and HR-MS. The aim of the modification was to enhance the cytotoxic and enzyme inhibitory effects of GA. 1,2,3,-Triazole substituted ferrocene (1), C-3 acetylated GA and the hybrid compound 3 were tested on A549, MCF-7, HCT-116, and PC-3 cancer cell lines. MCF-7 and HCT-116 cells showed the highest sensitivity to the compounds. Compound 3 showed more cytotoxicity than both GA and compound 1 with IC50 values of 23.97 and 50 µM in MCF-7 and HCT-116 cells, respectively. Morphological analysis indicated that compound 3 induced apoptotic cell death. In addition, the inhibitory effect of compounds on carbonic anhydrase I-II isoenzymes (hCAI-II), acetylcholinesterase/butyrylcholinesterase (AChE/BChE) enzymes, and α-glucosidase was tested. According to the results, compound 3, exhibited the strongest inhibitory properties for all enzymes tested with IC50 values of 0.0323, 0.3058, 0.0078, 0.0090 and 0.0120 µM, respectively. Molecular docking studies were performed to investigate the ligand-target protein interactions. Incorporating an organometallic sandwich-like compound ferrocene into GA via a 1,2,3-triazole bridge appears to be an effective strategy for modifying and enhancing its bioactivity.</div></div>","PeriodicalId":20278,"journal":{"name":"Polyhedron","volume":"279 ","pages":"Article 117620"},"PeriodicalIF":2.4000,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Polyhedron","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0277538725002347","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, INORGANIC & NUCLEAR","Score":null,"Total":0}

引用次数: 0

Abstract

18β-Glycyrrhetinic acid (GA) is a pentacyclic triterpene which was obtained from the roots of Glycyrrhiza glabra known for its diverse pharmaceutical applications. The primary aim of this study is to enhance the pharmaceutical properties of GA by modifying it with a 1,2,3-triazole-functionalized ferrocene moiety. The hybrid compound 3 was synthesized by amide functionalization of GA at the C-30 position with ferrocene, linked via a 1,4-disubstituted 1,2,3-triazole bridge. Additionally, the C-3 hydroxyl group of GA was converted into an acetyl ester. The hybrid compound 3 was characterized using FT-IR, NMR (¹H and ¹³C) and HR-MS. The aim of the modification was to enhance the cytotoxic and enzyme inhibitory effects of GA. 1,2,3,-Triazole substituted ferrocene (1), C-3 acetylated GA and the hybrid compound 3 were tested on A549, MCF-7, HCT-116, and PC-3 cancer cell lines. MCF-7 and HCT-116 cells showed the highest sensitivity to the compounds. Compound 3 showed more cytotoxicity than both GA and compound 1 with IC₅₀ values of 23.97 and 50 µM in MCF-7 and HCT-116 cells, respectively. Morphological analysis indicated that compound 3 induced apoptotic cell death. In addition, the inhibitory effect of compounds on carbonic anhydrase I-II isoenzymes (hCAI-II), acetylcholinesterase/butyrylcholinesterase (AChE/BChE) enzymes, and α-glucosidase was tested. According to the results, compound 3, exhibited the strongest inhibitory properties for all enzymes tested with IC₅₀ values of 0.0323, 0.3058, 0.0078, 0.0090 and 0.0120 µM, respectively. Molecular docking studies were performed to investigate the ligand-target protein interactions. Incorporating an organometallic sandwich-like compound ferrocene into GA via a 1,2,3-triazole bridge appears to be an effective strategy for modifying and enhancing its bioactivity.

查看原文本刊更多论文

新型三唑连接的二茂铁18β-甘草次酸杂化物的结构表征、细胞毒性和酶抑制谱

18β-甘草酸（glycyrrhetinic acid， GA）是一种从甘草根中提取的五环三萜，具有多种药用价值。本研究的主要目的是通过1,2,3-三唑功能化二茂铁片段修饰GA来增强其药物性能。杂化化合物3是由GA在C-30位置与二茂铁酰胺功能化合成的，并通过1,4-二取代1,2,3-三唑桥连接。此外，GA的C-3羟基转化为乙酰酯。利用FT-IR、NMR （1H和13C）和HR-MS对化合物3进行了表征。该修饰的目的是增强GA的细胞毒和酶抑制作用。对1,2,3，-三唑取代二茂铁(1)、C-3乙酰化GA和杂化化合物3在A549、MCF-7、HCT-116和PC-3癌细胞上进行了检测。MCF-7和HCT-116细胞对这些化合物的敏感性最高。化合物3对MCF-7和HCT-116细胞的IC50值分别为23.97和50µM，其细胞毒性高于GA和化合物1。形态学分析表明，化合物3可诱导凋亡细胞死亡。此外，还检测了化合物对碳酸酐酶I-II同工酶（hCAI-II）、乙酰胆碱酯酶/丁基胆碱酯酶（AChE/BChE）酶和α-葡萄糖苷酶的抑制作用。结果表明，化合物3对所有酶的抑制作用最强，IC50值分别为0.0323、0.3058、0.0078、0.0090和0.0120µM。通过分子对接研究来研究配体与靶蛋白的相互作用。通过1,2,3-三唑桥接将有机金属三明治状二茂铁化合物掺入GA中是修饰和提高其生物活性的有效策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Polyhedron 化学-晶体学

CiteScore

4.90

自引率

7.70%

发文量

515

审稿时长

2 months

期刊介绍： Polyhedron publishes original, fundamental, experimental and theoretical work of the highest quality in all the major areas of inorganic chemistry. This includes synthetic chemistry, coordination chemistry, organometallic chemistry, bioinorganic chemistry, and solid-state and materials chemistry. Papers should be significant pieces of work, and all new compounds must be appropriately characterized. The inclusion of single-crystal X-ray structural data is strongly encouraged, but papers reporting only the X-ray structure determination of a single compound will usually not be considered. Papers on solid-state or materials chemistry will be expected to have a significant molecular chemistry component (such as the synthesis and characterization of the molecular precursors and/or a systematic study of the use of different precursors or reaction conditions) or demonstrate a cutting-edge application (for example inorganic materials for energy applications). Papers dealing only with stability constants are not considered.