7-二乙氨基-4-氯甲基香豆素的合成与表征：光谱分析、分子对接以及对大肠癌细胞的抗癌活性。

IF 4.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemico-Biological Interactions Pub Date : 2024-10-22 DOI:10.1016/j.cbi.2024.111287

Hakan Beyaztas , Kubra Bozali , Sumeyye Koc , Mucahit Ozdemir , Bahattin Yalcin , Eray Metin Guler

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引用次数: 0

摘要

癌症以不受控制的细胞生长和转移为特征，给全球健康造成了巨大负担，是全球死亡的主要原因之一。结肠直肠癌（CRC）在癌症病例中占很大比例，预计未来几十年发病率将不断上升。虽然存在传统治疗方法，但这些方法往往会产生不良反应，而且疗效有限，因此人们对香豆素衍生物等天然疗法产生了兴趣，因为它们具有多种生物活性，而且安全可靠。本研究侧重于从香豆素中提取的新型化合物--7-二乙氨基-4-氯甲基香豆素（简称 7D4C）的合成和表征。结构阐释采用了傅立叶变换红外光谱（FT-IR）、质子和碳 13 核磁共振光谱（1H 和 13C NMR）以及质谱分析（MALDI-TOF-MS）。还进行了分子对接研究，以探索潜在的生物相互作用。此外，还利用人体上皮腺癌细胞系（LoVo）和健康成纤维细胞系（CCD-18Co）评估了 7D4C 的抗癌潜力。研究人员进行了细胞活力分析、DNA 损伤彗星试验以及癌症生物标志物评估，包括细胞凋亡、细胞内活性氧（iROS）水平、线粒体膜电位（MMP）、细胞内谷胱甘肽（GSH）浓度和细胞内钙（iCa2+）水平。成功完成了 7D4C 的合成，并确认了其结构。分子对接结果表明，7D4C 与 p53 蛋白具有很强的结合亲和力，这凸显了它作为一种新型 p53 活性调节剂的潜力。随后的研究发现，合成的化合物通过减少 MMP 和产生 iROS 引发 DNA 损伤，从而诱导癌细胞凋亡。7D4C 在 LoVo 细胞系中具有良好的抗癌活性，这凸显了它在香豆素疗法中的重要性。引入 7D4C 可以利用体外香豆素研究的洞察力，大大加强该领域的未来研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Synthesis and characterization of 7-diethylamino-4-Chloromethyl coumarin: Spectroscopic analysis, molecular docking, and anticancer activity on large intestine carcinoma cells

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Synthesis and characterization of 7-diethylamino-4-Chloromethyl coumarin: Spectroscopic analysis, molecular docking, and anticancer activity on large intestine carcinoma cells

Cancer, characterized by uncontrolled cell growth and metastasis, poses a significant global health burden, ranking as a leading cause of mortality worldwide. Colorectal cancer (CRC) specifically accounts for a substantial portion of cancer cases, with increasing incidence projected over the coming decades. While conventional treatments exist, they often entail adverse effects and limited efficacy, driving interest in natural remedies like coumarin derivatives due to their diverse biological activities and perceived safety profile. This study focuses on the synthesis and characterization of a novel compound, 7-diethylamino-4-chloromethyl coumarin (referred to as 7D4C), derived from coumarin. Structural elucidation employed Fourier transform infrared spectroscopy (FT-IR), proton and carbon-13 nuclear magnetic resonance spectroscopy (¹H and ¹³C NMR), and mass spectrometry (MALDI-TOF-MS). Molecular docking studies were conducted to explore potential biological interactions. Furthermore, the anti-cancer potential of 7D4C was assessed using human epithelial adenocarcinom (LoVo) and healthy fibroblast (CCD-18Co) cell lines. Viability analysis, comet assay for DNA damage, and evaluation of cancer biomarkers including apoptosis, intracellular reactive oxygen species (iROS) levels, mitochondrial membrane potential (MMP), intracellular glutathione (GSH) concentration, and intracellular calcium (iCa²⁺) levels were performed. The synthesis of 7D4C was successfully completed, and its structure was confirmed. Molecular docking results indicate that 7D4C exhibits strong binding affinity to the p53 protein, highlighting its potential as a novel modulator of p53 activity. Subsequent investigations revealed that the synthesized compound induced apoptosis in cancer cells by reducing MMP and triggering DNA damage through the production of iROS. The promising anti-cancer activity of 7D4C in the LoVo cell line highlights its importance in coumarin-based therapies. Introducing 7D4C could significantly enhance future research in this area, leveraging insights from in vitro coumarin studies.

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来源期刊

Chemico-Biological Interactions 生物-毒理学

CiteScore

7.70

自引率

3.90%

发文量

410

审稿时长

36 days

期刊介绍： Chemico-Biological Interactions publishes research reports and review articles that examine the molecular, cellular, and/or biochemical basis of toxicologically relevant outcomes. Special emphasis is placed on toxicological mechanisms associated with interactions between chemicals and biological systems. Outcomes may include all traditional endpoints caused by synthetic or naturally occurring chemicals, both in vivo and in vitro. Endpoints of interest include, but are not limited to carcinogenesis, mutagenesis, respiratory toxicology, neurotoxicology, reproductive and developmental toxicology, and immunotoxicology.