Department of Chemistry, Government College of Engineering, Sengipatti, Thanjavur, 613402, Tamil Nadu, India.
Division of Phytochemistry and Drug Design, Department of Biosciences, Rajagiri College of Social Sciences, Cochin, 683104, Kerala, India.
Appl Biochem Biotechnol. 2024 Aug;196(8):5447-5470. doi: 10.1007/s12010-023-04803-4. Epub 2023 Dec 30.
Alzheimer's disease (AD) is an extremely complex, heterogeneous, and multifactorial neurodegenerative disease clinically characterized by progressive memory loss and progressive decline in cognitive function. There is currently no effective treatment for the onset and/or progression of the pathophysiological diseases of AD. The global prevalence of this disease has increased in recent years due to modern lifestyle. Therefore, there is an urgent need to develop a drug with significant neuroprotective potential. Since plant metabolites, especially polyphenols, have important pharmacological properties acting against β-amyloid (Aβ), Tau, neuroinflammation, and oxidative stress, such phytochemicals were selected in the present research. Using the Schrödinger tool (Maestro V.13.6), the drug potency of these metabolites was studied after installation in the highly configured workstation. Among the 120 polyphenols docked, amygdalin showed notable docking values of - 11.2638, followed by eriocitrin (- 10.9569), keracyanin (- 10.7086), and amaroswerin (- 9.48126). The prominent MM-GBSA values of these molecules were - 62.8829, - 52.1914, - 68.6307, and - 63.1074, respectively. The MM-GBSA energy values demonstrated the drug stability of these molecules for β-site amyloid precursor protein-cleaving enzyme 1 (BACE1)-causing AD. In the absorption and distribution assessment, these phytochemicals showed significantly better values than the inhibitors CNP520. The chosen phytochemicals have been demonstrated as non-hepatotoxic; however, the BACE1 inhibitor CNP520 is hepatotoxic. In both the molecular docking and ADMET assessments, these natural chemicals have shown optimism as potential drug candidates for Alzheimer's disease. However, in order to understand the detailed biological metabolism of these compounds in AD, they need to be evaluated in in vivo studies to validate its efficacy.
阿尔茨海默病（AD）是一种极其复杂、异质和多因素的神经退行性疾病，临床上表现为进行性记忆丧失和认知功能逐渐下降。目前尚无针对 AD 病理生理疾病发病和/或进展的有效治疗方法。由于现代生活方式，近年来这种疾病的全球患病率有所增加。因此，迫切需要开发具有显著神经保护潜力的药物。由于植物代谢物，特别是多酚，具有针对β-淀粉样蛋白（Aβ）、Tau、神经炎症和氧化应激的重要药理特性，因此在本研究中选择了这些植物化学物质。使用 Schrödinger 工具（Maestro V.13.6），在高度配置的工作站中安装这些代谢物后，研究了它们的药物效力。在对接的 120 种多酚中，苦杏仁苷表现出显著的对接值-11.2638，其次是桔皮苷（-10.9569）、圣草酚（-10.7086）和异荭草苷（-9.48126）。这些分子的突出 MM-GBSA 值分别为-62.8829、-52.1914、-68.6307 和-63.1074。MM-GBSA 能量值表明这些分子对β-位淀粉样前体蛋白切割酶 1（BACE1）引起的 AD 具有药物稳定性。在吸收和分布评估中，这些植物化学物质显示出比抑制剂 CNP520 更好的数值。所选植物化学物质已被证明是非肝毒性的；然而，BACE1 抑制剂 CNP520 是肝毒性的。在分子对接和 ADMET 评估中，这些天然化学物质均表现出乐观的态势，有望成为治疗阿尔茨海默病的潜在药物候选物。然而，为了了解这些化合物在 AD 中的详细生物学代谢，需要在体内研究中对其进行评估，以验证其疗效。
