Departamento de Farmacia, DCNE, Universidad de Guanajuato, Noria Alta S/N. Col. Noria Alta, Gto., C. P. 36050, Guanajuato, México.
J Mol Model. 2022 Feb 26;28(3):68. doi: 10.1007/s00894-022-05056-4.
The antiradical properties and possible mechanisms of action of the tautomers of curcumin, caffeic acid phenethyl ester (CAPE), and chicoric acid (CA) have been studied within density functional theory (DFT). We calculated global chemical reactivity descriptors from conceptual DFT, pK, bioavailability, and toxicity to evaluate the antiradical properties and characterize these species. Our final level of theory is the M06-2X functional with the 6-31 + G* basis set; we selected this level after performing a benchmark calibration and validation among different levels. Solvent effects were modeled via the continuum solvation model based on density (SMD). We used water and pentyl ethanoate as solvents to simulate the physiological conditions. The free radical scavenger capacity was analyzed for three possible oxidative stress mechanisms: single electron transfer (SET), hydrogen atom transfer (HAT), and xanthine oxidase (XO) inhibition. The results indicate that neutral curcumin, CA, and CAPE behave as antireductants. The most favorable mechanism turns out to be HAT, where CA and CAPE stand out. In conclusion, our DFT study strongly indicates that neutral curcumin, CAPE, and CA would very likely perform well as antiradical drugs with recommended therapeutic use, supported by their non-toxic nature.
我们运用密度泛函理论（DFT）研究了姜黄素、咖啡酸苯乙酯（CAPE）和菊苣酸（CA）互变异构体的抗自由基特性及其可能的作用机制。我们从概念性 DFT 计算了全球化学反应性描述符、pK 值、生物利用度和毒性，以评估抗自由基特性并对这些物质进行了表征。我们最终的理论水平是 M06-2X 功能和 6-31G*基组；在不同水平之间进行基准校准和验证后，我们选择了这个水平。通过基于密度的连续溶剂化模型（SMD）模拟溶剂效应。我们使用水和戊基乙酸酯作为溶剂来模拟生理条件。分析了三种可能的氧化应激机制的自由基清除能力：单电子转移（SET）、氢原子转移（HAT）和黄嘌呤氧化酶（XO）抑制。结果表明，中性姜黄素、CA 和 CAPE 表现为抗氧化剂。最有利的机制是 HAT，其中 CA 和 CAPE 脱颖而出。总之，我们的 DFT 研究强烈表明，中性姜黄素、CAPE 和 CA 很可能作为抗自由基药物发挥良好作用，并具有推荐的治疗用途，这得益于它们的无毒性质。
