{"title":"揭示一种新型铬烯衍生物与 DNA 之间的分子相互作用:一项多方面的研究","authors":"Dipak Kumar Sahoo, Nilima Priyadarsini Mishra, Shamasoddin Shekh, Emmanuel E. Etim","doi":"10.1007/s11696-024-03654-5","DOIUrl":null,"url":null,"abstract":"<div><p>This study comprehensively investigates the interactions between a new chromene derivative, 8-methoxy-3-nitro-2-(4-methoxyphenyl)-2H-chromene (MMNC), and DNA using a combination of experimental and computational techniques. MTT assays demonstrated MMNC’s potent anticancer activity against various cell lines, with lower IC50 values than the clinically used drug 5-fluorouracil. Spectroscopic techniques including circular dichroism, dynamic light scattering, UV–visible absorption, and fluorescence quenching experiments revealed that MMNC interacts with DNA at its minor groove without significantly altering its overall structure. The binding constant (Ka) was determined to be 3.09 × 10<sup>3</sup> M<sup>−1</sup>, indicating moderate groove binding. Molecular docking simulations supported the experimental findings, showing MMNC favorably binds to the DNA minor groove with a docking score of − 2.5 kcal/mol and binding free energy of − 26 kcal/mol. DFT studies provided insights into MMNC's electronic properties, with a HOMO–LUMO energy gap of 3.14 eV suggesting good reactivity. ADME/Tox analysis confirmed MMNC's drug-like properties, with no violations of Lipinski's rule of five or Jorgensen's rule of three. 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引用次数: 0
摘要
本研究结合实验和计算技术,全面研究了一种新的色烯衍生物--8-甲氧基-3-硝基-2-(4-甲氧基苯基)-2H-色烯(MMNC)与 DNA 之间的相互作用。MTT 试验证明 MMNC 对多种细胞株具有强效抗癌活性,其 IC50 值低于临床常用药物 5-氟尿嘧啶。包括圆二色性、动态光散射、紫外可见吸收和荧光淬灭实验在内的光谱技术表明,MMNC 与 DNA 的次沟相互作用,而不会明显改变其整体结构。结合常数(Ka)被测定为 3.09 × 103 M-1,表明它与 DNA 有中等程度的沟结合。分子对接模拟支持了实验结果,显示 MMNC 与 DNA 小沟结合良好,对接得分为 - 2.5 kcal/mol,结合自由能为 - 26 kcal/mol。DFT 研究深入揭示了 MMNC 的电子特性,其 HOMO-LUMO 能隙为 3.14 eV,表明其具有良好的反应性。ADME/Tox 分析证实了 MMNC 的类药物特性,没有违反利宾斯基的五法则或乔根森的三法则。综合结果表明 MMNC 具有作为抗癌剂的巨大潜力,并为合理设计改进的铬基药物奠定了基础。
Unveiling the molecular interplay between a novel chromene derivative and DNA: a multifaceted investigation
This study comprehensively investigates the interactions between a new chromene derivative, 8-methoxy-3-nitro-2-(4-methoxyphenyl)-2H-chromene (MMNC), and DNA using a combination of experimental and computational techniques. MTT assays demonstrated MMNC’s potent anticancer activity against various cell lines, with lower IC50 values than the clinically used drug 5-fluorouracil. Spectroscopic techniques including circular dichroism, dynamic light scattering, UV–visible absorption, and fluorescence quenching experiments revealed that MMNC interacts with DNA at its minor groove without significantly altering its overall structure. The binding constant (Ka) was determined to be 3.09 × 103 M−1, indicating moderate groove binding. Molecular docking simulations supported the experimental findings, showing MMNC favorably binds to the DNA minor groove with a docking score of − 2.5 kcal/mol and binding free energy of − 26 kcal/mol. DFT studies provided insights into MMNC's electronic properties, with a HOMO–LUMO energy gap of 3.14 eV suggesting good reactivity. ADME/Tox analysis confirmed MMNC's drug-like properties, with no violations of Lipinski's rule of five or Jorgensen's rule of three. The comprehensive results demonstrate MMNC's promising potential as an anticancer agent and provide a foundation for rational design of improved chromene-based drugs.
Chemical PapersChemical Engineering-General Chemical Engineering
CiteScore
3.30
自引率
4.50%
发文量
590
期刊介绍:
Chemical Papers is a peer-reviewed, international journal devoted to basic and applied chemical research. It has a broad scope covering the chemical sciences, but favors interdisciplinary research and studies that bring chemistry together with other disciplines.