The <i>Cordyceps</i> Genus as a Potential Source of Bioactive Compounds for Adjuvant Cancer Therapy: A Network Pharmacology Approach

<b>Background/Objectives:</b> 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 &...

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Main Authors: Jose Luis Gonzalez-Llerena, Daniela Treviño-Almaguer, Jesus Alejandro Leal-Mendez, Gael Garcia-Valdez, Arely Guadalupe Balderas-Moreno, Michel Stéphane Heya, Isaias Balderas-Renteria, María del Rayo Camacho-Corona, Bryan Alejandro Espinosa-Rodriguez
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Language:English
Published: MDPI AG 2025-04-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/18/5/667
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author Jose Luis Gonzalez-Llerena
Daniela Treviño-Almaguer
Jesus Alejandro Leal-Mendez
Gael Garcia-Valdez
Arely Guadalupe Balderas-Moreno
Michel Stéphane Heya
Isaias Balderas-Renteria
María del Rayo Camacho-Corona
Bryan Alejandro Espinosa-Rodriguez
author_facet Jose Luis Gonzalez-Llerena
Daniela Treviño-Almaguer
Jesus Alejandro Leal-Mendez
Gael Garcia-Valdez
Arely Guadalupe Balderas-Moreno
Michel Stéphane Heya
Isaias Balderas-Renteria
María del Rayo Camacho-Corona
Bryan Alejandro Espinosa-Rodriguez
author_sort Jose Luis Gonzalez-Llerena
collection DOAJ
description <b>Background/Objectives:</b> 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 <i>Cordyceps</i>, represent promising candidates due to their diverse biological activities. Although previous studies have indicated the anticancer potential of <i>Cordyceps</i> species, systematic characterization of their molecular targets has been limited. This study aimed to comprehensively identify and evaluate <i>Cordyceps</i> metabolites as potential multitarget anticancer agents through a network pharmacology approach. <b>Methods:</b> A total of 129 metabolites previously reported in the literature from polar aqueous, alcoholic, and non-polar extracts of <i>Cordyceps</i> 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. <b>Results:</b> The analysis revealed that <i>Cordyceps</i> 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. <b>Conclusions:</b><i>Cordyceps</i> 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.
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spelling doaj-art-5b8d867874964d259dfd636a698fba8c2025-08-20T03:48:01ZengMDPI AGPharmaceuticals1424-82472025-04-0118566710.3390/ph18050667The <i>Cordyceps</i> Genus as a Potential Source of Bioactive Compounds for Adjuvant Cancer Therapy: A Network Pharmacology ApproachJose Luis Gonzalez-Llerena0Daniela Treviño-Almaguer1Jesus Alejandro Leal-Mendez2Gael Garcia-Valdez3Arely Guadalupe Balderas-Moreno4Michel Stéphane Heya5Isaias Balderas-Renteria6María del Rayo Camacho-Corona7Bryan Alejandro Espinosa-Rodriguez8Laboratory of Molecular Pharmacology and Biological Models, School of Chemistry, Universidad Autonoma de Nuevo Leon, Monterrey 64570, Nuevo Leon, MexicoLaboratory of Molecular Pharmacology and Biological Models, School of Chemistry, Universidad Autonoma de Nuevo Leon, Monterrey 64570, Nuevo Leon, MexicoLaboratory of Molecular Pharmacology and Biological Models, School of Chemistry, Universidad Autonoma de Nuevo Leon, Monterrey 64570, Nuevo Leon, MexicoLaboratory of Molecular Pharmacology and Biological Models, School of Chemistry, Universidad Autonoma de Nuevo Leon, Monterrey 64570, Nuevo Leon, MexicoLaboratory of Molecular Pharmacology and Biological Models, School of Chemistry, Universidad Autonoma de Nuevo Leon, Monterrey 64570, Nuevo Leon, MexicoFaculty of Public Health and Nutrition, Universidad Autonoma de Nuevo Leon, Monterrey 64460, Nuevo Leon, MexicoLaboratory of Molecular Pharmacology and Biological Models, School of Chemistry, Universidad Autonoma de Nuevo Leon, Monterrey 64570, Nuevo Leon, MexicoLaboratory of Pharmaceutical Chemistry, School of Chemistry, Universidad Autonoma de Nuevo Leon, Monterrey 64570, Nuevo Leon, MexicoLaboratory of Biopharmacy, School of Chemistry, Universidad Autonoma de Nuevo Leon, San Nicolas de los Garza 66451, Nuevo Leon, Mexico<b>Background/Objectives:</b> 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 <i>Cordyceps</i>, represent promising candidates due to their diverse biological activities. Although previous studies have indicated the anticancer potential of <i>Cordyceps</i> species, systematic characterization of their molecular targets has been limited. This study aimed to comprehensively identify and evaluate <i>Cordyceps</i> metabolites as potential multitarget anticancer agents through a network pharmacology approach. <b>Methods:</b> A total of 129 metabolites previously reported in the literature from polar aqueous, alcoholic, and non-polar extracts of <i>Cordyceps</i> 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. <b>Results:</b> The analysis revealed that <i>Cordyceps</i> 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. <b>Conclusions:</b><i>Cordyceps</i> 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.https://www.mdpi.com/1424-8247/18/5/667<i>Cordyceps</i>network pharmacologycancer therapeuticsmolecular dockingmetabolite profilingdrug resistance
spellingShingle Jose Luis Gonzalez-Llerena
Daniela Treviño-Almaguer
Jesus Alejandro Leal-Mendez
Gael Garcia-Valdez
Arely Guadalupe Balderas-Moreno
Michel Stéphane Heya
Isaias Balderas-Renteria
María del Rayo Camacho-Corona
Bryan Alejandro Espinosa-Rodriguez
The <i>Cordyceps</i> Genus as a Potential Source of Bioactive Compounds for Adjuvant Cancer Therapy: A Network Pharmacology Approach
Pharmaceuticals
<i>Cordyceps</i>
network pharmacology
cancer therapeutics
molecular docking
metabolite profiling
drug resistance
title The <i>Cordyceps</i> Genus as a Potential Source of Bioactive Compounds for Adjuvant Cancer Therapy: A Network Pharmacology Approach
title_full The <i>Cordyceps</i> Genus as a Potential Source of Bioactive Compounds for Adjuvant Cancer Therapy: A Network Pharmacology Approach
title_fullStr The <i>Cordyceps</i> Genus as a Potential Source of Bioactive Compounds for Adjuvant Cancer Therapy: A Network Pharmacology Approach
title_full_unstemmed The <i>Cordyceps</i> Genus as a Potential Source of Bioactive Compounds for Adjuvant Cancer Therapy: A Network Pharmacology Approach
title_short The <i>Cordyceps</i> Genus as a Potential Source of Bioactive Compounds for Adjuvant Cancer Therapy: A Network Pharmacology Approach
title_sort i cordyceps i genus as a potential source of bioactive compounds for adjuvant cancer therapy a network pharmacology approach
topic <i>Cordyceps</i>
network pharmacology
cancer therapeutics
molecular docking
metabolite profiling
drug resistance
url https://www.mdpi.com/1424-8247/18/5/667
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