这项研究的主要目的是发现治疗多形性胶质母细胞瘤（GBM）（一种高度侵袭性脑癌）和阿尔茨海默病（AD）的新型治疗药物。考虑到这两种疾病的复杂性和耐药性，该研究强调迫切需要能够克服神经肿瘤和神经退行性疾病固有的生物学复杂性的治疗替代方案。为了实现这一目标，我们对主要源自植物来源的 50 种黄酮类化合物和多酚衍生物进行了细致的、基于目标的虚拟筛选。筛选主要集中于与 GBM 相关的分子靶标，但也评估了与 AD 相关神经通路的潜在重叠。该研究利用分子对接和分子动力学 (MD) 模拟技术来分析这些化合物与关键生物靶标 Z 型蛋白酪氨酸磷酸酶受体 (PTPRZ) 的相互作用。在检查的 50 种化合物中，有 10 种符合我们严格的结合亲和力和特异性标准。随后，观察到木犀草素和阿魏酸协同结合的最高结合能值为-10.5 kcal/mol。这两种化合物均表现出固有的神经保护特性，并显示出作为 GBM 通路抑制剂以及 AD 分子调节剂的巨大潜力。这项研究利用先进的计算机细胞毒性预测和复杂的分子建模技术，重点关注多酚对 GBM 的治疗能力。此外，我们的研究结果表明，利用这些化合物可以催化急需的范式转变，转向更综合的治疗方法，涵盖神经肿瘤学和神经退行性疾病的广度。类黄酮和多酚的交叉治疗潜力的鉴定可以极大地扩大针对这两种致命疾病的治疗方式的范围。版权所有：© 2023 Suhail 等人。这是一篇根据知识共享署名许可条款分发的开放获取文章，允许在任何媒体上不受限制地使用、分发和复制，前提是注明原始作者和来源。

The primary objective of this study is to uncover novel therapeutic agents for the treatment of Glioblastoma Multiforme (GBM), a highly aggressive form of brain cancer, and Alzheimer's Disease (AD). Given the complexity and resistance associated with both conditions, the study underscores the imperative need for therapeutic alternatives that can traverse the biological intricacies inherent in both neuro-oncological and neurodegenerative disorders. To achieve this, a meticulous, target-based virtual screening was employed on an ensemble of 50 flavonoids and polyphenol derivatives primarily derived from plant sources. The screening focused predominantly on molecular targets pertinent to GBM but also evaluated the potential overlap with neural pathways involved in AD. The study utilized molecular docking and Molecular Dynamic (MD) simulation techniques to analyze the interaction of these compounds with a key biological target, protein tyrosine phosphatase receptor-type Z (PTPRZ). Out of the 50 compounds examined, 10 met our stringent criteria for binding affinity and specificity. Subsequently, the highest value of binding energy was observed for the synergistic binding of luteolin and ferulic acid with the value of -10.5 kcal/mol. Both compounds exhibited inherent neuroprotective properties and demonstrated significant potential as pathway inhibitors in GBM as well as molecular modulators in AD. Drawing upon advanced in-silico cytotoxicity predictions and sophisticated molecular modeling techniques, this study casts a spotlight on the therapeutic capabilities of polyphenols against GBM. Furthermore, our findings suggest that leveraging these compounds could catalyze a much-needed paradigm shift towards more integrative therapeutic approaches that span the breadth of both neuro-oncology and neurodegenerative diseases. The identification of cross-therapeutic potential in flavonoids and polyphenols could drastically broaden the scope of treatment modalities against both fatal diseases.Copyright: © 2023 Suhail et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.