Gonzalez-Llerena Jose Luis, Treviño-Almaguer Daniela, Leal-Mendez Jesus Alejandro, Garcia-Valdez Gael, Balderas-Moreno Arely Guadalupe, Heya Michel Stéphane, Balderas-Renteria Isaias, Camacho-Corona María Del Rayo, Espinosa-Rodriguez Bryan Alejandro
Laboratory of Molecular Pharmacology and Biological Models, School of Chemistry, Universidad Autonoma de Nuevo Leon, Monterrey 64570, Nuevo Leon, Mexico.
Faculty of Public Health and Nutrition, Universidad Autonoma de Nuevo Leon, Monterrey 64460, Nuevo Leon, Mexico.
Pharmaceuticals (Basel). 2025 Apr 30;18(5):667. doi: 10.3390/ph18050667.
Cancer remains one of the leading causes of mortality globally, underscoring the need for novel therapeutic strategies capable of targeting multiple molecular pathways simultaneously. Natural products, particularly fungal-derived metabolites from the genus , represent promising candidates due to their diverse biological activities. Although previous studies have indicated the anticancer potential of species, systematic characterization of their molecular targets has been limited. This study aimed to comprehensively identify and evaluate metabolites as potential multitarget anticancer agents through a network pharmacology approach. A total of 129 metabolites previously reported in the literature from polar aqueous, alcoholic, and non-polar extracts of were compiled and chemically classified using ChemMine tools. Structure-based target prediction and pathway enrichment analyses were performed to investigate their potential biological targets. Predicted molecular targets were cross-referenced with differentially expressed genes in breast, colorectal, and lung cancers to identify hub proteins. Molecular docking simulations were conducted to assess binding affinities of metabolites to key oncogenic targets, and SwissADME was utilized for pharmacokinetic profiling. The analysis revealed that metabolites targeted critical oncogenic pathways, including cell cycle regulation, DNA replication, and apoptosis. Hub proteins such as TYMS, AURKA, and CDK1 were identified as primary targets. Docking simulations highlighted metabolites such as cordycepsidone A, jiangxienone, and flazin, demonstrating binding affinities comparable or superior to clinically used inhibitors. Pharmacokinetic profiling identified several metabolites with favorable drug-like properties, supporting their potential as lead compounds. extracts contain structurally diverse metabolites capable of modulating multiple cancer-relevant molecular targets, providing a robust foundation for their development into multitarget anticancer therapies. This integrative network pharmacology approach underscores the potential of fungal metabolites in oncology drug discovery.
癌症仍然是全球主要的死亡原因之一，这凸显了对能够同时靶向多种分子途径的新型治疗策略的需求。天然产物，特别是来自该属的真菌衍生代谢产物，由于其多样的生物活性而成为有前景的候选物。尽管先前的研究表明该物种具有抗癌潜力，但其分子靶点的系统表征仍然有限。本研究旨在通过网络药理学方法全面鉴定和评估该代谢产物作为潜在的多靶点抗癌剂。总共收集了先前文献中报道的来自该属极性水提取物、醇提取物和非极性提取物中的129种代谢产物，并使用ChemMine工具进行化学分类。进行基于结构的靶点预测和通路富集分析以研究其潜在的生物学靶点。将预测的分子靶点与乳腺癌、结直肠癌和肺癌中的差异表达基因进行交叉参考以鉴定枢纽蛋白。进行分子对接模拟以评估代谢产物与关键致癌靶点的结合亲和力，并利用SwissADME进行药代动力学分析。分析表明该代谢产物靶向关键的致癌途径，包括细胞周期调控、DNA复制和细胞凋亡。TYMS、AURKA和CDK1等枢纽蛋白被确定为主要靶点。对接模拟突出了如虫草素A、江西新酮和黄酮等代谢产物，其显示出与临床使用的抑制剂相当或更高的结合亲和力。药代动力学分析鉴定了几种具有良好类药性质的代谢产物，支持它们作为先导化合物的潜力。该属提取物含有能够调节多种癌症相关分子靶点的结构多样的代谢产物，为将其开发为多靶点抗癌疗法提供了坚实的基础。这种综合的网络药理学方法强调了真菌代谢产物在肿瘤药物发现中的潜力。
