Ancuceanu Robert, Lascu Beatrice Elena, Drăgănescu Doina, Dinu Mihaela
Faculty of Pharmacy, Department of Pharmaceutical Botany and Cell Biology, Carol Davila University of Medicine and Pharmacy, 050474 București, Romania.
Faculty of Pharmacy, Department of Pharmaceutical Physics and Informatics, Carol Davila University of Medicine and Pharmacy, 050474 București, Romania.
Pharmaceutics. 2025 Jul 31;17(8):1002. doi: 10.3390/pharmaceutics17081002.
The pharmaceutical industry faces significant challenges when promising drug candidates fail during development due to suboptimal ADME (absorption, distribution, metabolism, excretion) properties or toxicity concerns. Natural compounds are subject to the same pharmacokinetic considerations. In silico approaches offer a compelling advantage-they eliminate the need for physical samples and laboratory facilities, while providing rapid and cost-effective alternatives to expensive and time-consuming experimental testing. Computational methods can often effectively address common challenges associated with natural compounds, such as chemical instability and poor solubility. Through a review of the relevant scientific literature, we present a comprehensive analysis of in silico methods and tools used for ADME prediction, specifically examining their application to natural compounds. Whereas we focus on identifying the predominant computational approaches applicable to natural compounds, these tools were developed for conventional drug discovery and are of general use. We examine an array of computational approaches for evaluating natural compounds, including fundamental methods like quantum mechanics calculations, molecular docking, and pharmacophore modeling, as well as more complex techniques such as QSAR analysis, molecular dynamics simulations, and PBPK modeling.
当有前景的候选药物由于不理想的药物代谢动力学（吸收、分布、代谢、排泄）特性或毒性问题在研发过程中失败时，制药行业面临重大挑战。天然化合物也面临同样的药代动力学考量。计算机模拟方法具有显著优势——它们无需实物样本和实验室设施，同时为昂贵且耗时的实验测试提供了快速且经济高效的替代方案。计算方法通常能够有效应对与天然化合物相关的常见挑战，如化学不稳定性和低溶解度。通过对相关科学文献的综述，我们对用于药物代谢动力学预测的计算机模拟方法和工具进行了全面分析，特别考察了它们在天然化合物中的应用。虽然我们专注于确定适用于天然化合物的主要计算方法，但这些工具是为传统药物研发而开发的，具有普遍适用性。我们研究了一系列用于评估天然化合物的计算方法，包括量子力学计算、分子对接和药效团建模等基础方法，以及更复杂的技术，如定量构效关系分析、分子动力学模拟和生理药代动力学建模。
