Molecular Docking Appraisal of Pleurotus ostreatus Phytochemicals as Potential Inhibitors of PI3K/Akt Pathway for Breast Cancer Treatment.

IF 2.3 Q3 BIOCHEMICAL RESEARCH METHODS
Bioinformatics and Biology Insights Pub Date : 2025-02-03 eCollection Date: 2025-01-01 DOI:10.1177/11779322251316864
Magdalene Eno Effiong, Mercy Bella-Omunagbe, Israel Sunmola Afolabi, Shalom Nwodo Chinedu
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引用次数: 0

Abstract

Introduction: Breast cancer (BC) is a heterogeneous disease involving a network of numerous extracellular signal transduction pathways. The phosphoinositide 3-kinase (PI3K)/serine/threonine kinase (Akt)/mechanistic target of rapamycin (mTOR) pathway is crucial for understanding the BC development. Phosphoinositide 3-kinase, phosphatase and tensin homolog (PTEN), mTOR, Akt, 3-phosphoinositide-dependent kinase 1 (PDK1), FoxO1, glycogen synthase kinase 3 (GSK-3), mouse double minute 2 (MDM2), H-Ras, and proapoptotic B-cell lymphoma 2 (BCL-2) family protein (BAD) proteins are key drivers of this pathway and potential therapeutic targets. Pleurotus ostreatus is an edible mushroom that is rich in flavonoids and phenols that can serve as potential inhibitors of proteins in the PI3K/Akt/mTOR pathway.

Aim: This study evaluated the anticancer properties of P ostreatus through a structure-based virtual screening of 22 biologically active compounds present in the mushroom.

Method: Model optimization was carried out on PI3K, PTEN, mTOR, Akt, PDK1, FoxO1, GSK-3, MDM2, H-Ras, and BAD proteins in the PI3K/Akt/mTOR pathway and molecular docking of compounds/control inhibitors in the binding pocket were simulated AutoDock Vina in PyRx. The drug likeness, pharmacokinetic, and pharmacodynamic features of prospective docking leads were all anticipated.

Result: Several potent inhibitors of the selected key driver proteins in PI3K/Akt/mTOR pathway were identified from P ostreatus. Ellagic acid with binding affinities of -8.0, -8.0, -8.1, -8.2, -6.2, and -7.1 kcal/mol on PI3K, Akt, PDK1, GSK-3, MDM2, and BAD, respectively, had better binding affinity compared with their reference drugs. Likewise, apigenin (-7.8 kcal/mol), chrysin (-7.8 kcal/mol), quercetin (-6.4 kcal/mol), and chlorogenic acid (-6.2 kcal/mol) had better binding affinities to PTEN, mTOR, FoxO1, and H-Ras proteins, respectively.

Conclusion: Ellagic acid, apigenin, luteolin, quercetin, chlorogenic acid, chrysin, and naringenin phytochemicals are seen as the better lead molecules due to their ability to strongly bind to the proteins under study in this pathway. Analogs of these compounds can also be designed as potential drugs.

平耳植物化学物质作为PI3K/Akt通路潜在抑制剂治疗乳腺癌的分子对接评价
乳腺癌(BC)是一种异质性疾病,涉及许多细胞外信号转导通路网络。phosphoinositide 3-kinase (PI3K)/serine/苏氨酸激酶(Akt)/mechanistic target of rapamycin (mTOR) pathway对于了解BC的发展至关重要。磷酸肌苷3-激酶、磷酸酶和紧张素同源物(PTEN)、mTOR、Akt、3-磷酸肌苷依赖性激酶1 (PDK1)、FoxO1、糖原合成酶激酶3 (GSK-3)、小鼠双分钟2 (MDM2)、H-Ras和促凋亡b细胞淋巴瘤2 (BCL-2)家族蛋白(BAD)蛋白是该途径的关键驱动因素和潜在的治疗靶点。平菇是一种富含类黄酮和酚类物质的食用菌,可以作为PI3K/Akt/mTOR通路中蛋白质的潜在抑制剂。目的:本研究通过对蘑菇中22种生物活性化合物的结构虚拟筛选来评价其抗癌特性。方法:对PI3K/Akt/mTOR通路中的PI3K、PTEN、mTOR、Akt、PDK1、FoxO1、GSK-3、MDM2、H-Ras和BAD蛋白进行模型优化,并在PyRx中模拟AutoDock Vina中结合袋中化合物/控制抑制剂的分子对接。预期对接导线的药物相似性、药代动力学和药效学特征都得到了预测。结果:从P ostreatus中鉴定出PI3K/Akt/mTOR通路关键驱动蛋白的几种有效抑制剂。鞣花酸对PI3K、Akt、PDK1、GSK-3、MDM2和BAD的结合亲和力分别为-8.0、-8.0、-8.1、-8.2、-6.2和-7.1 kcal/mol,与参比药物相比具有更好的结合亲和力。同样,芹菜素(-7.8 kcal/mol)、白藜芦醇(-7.8 kcal/mol)、槲皮素(-6.4 kcal/mol)和绿原酸(-6.2 kcal/mol)与PTEN、mTOR、FoxO1和H-Ras蛋白的结合亲和力较好。结论:鞣花酸、芹菜素、木犀草素、槲皮素、绿原酸、菊花素和柚皮素等植物化学物质可以与该途径中研究的蛋白质强结合,因此被认为是较好的先导分子。这些化合物的类似物也可以被设计成潜在的药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Bioinformatics and Biology Insights
Bioinformatics and Biology Insights BIOCHEMICAL RESEARCH METHODS-
CiteScore
6.80
自引率
1.70%
发文量
36
审稿时长
8 weeks
期刊介绍: Bioinformatics and Biology Insights is an open access, peer-reviewed journal that considers articles on bioinformatics methods and their applications which must pertain to biological insights. All papers should be easily amenable to biologists and as such help bridge the gap between theories and applications.
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