Evaluation of Antifibrotic Mechanisms of 3′5-Dimaleamylbenzoic Acid on Idiopathic Pulmonary Fibrosis: A Network Pharmacology and Molecular Docking Analysis
Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, disabling disorder of unknown etiology, poor prognosis, and limited therapeutic options. Previously, 3′5-dimaleamylbenzoic acid (3′5-DMBA) was shown to exert resolving effects in IPF, offering a promising alternative for treating this dis...
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MDPI AG
2024-12-01
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| Online Access: | https://www.mdpi.com/2813-2998/3/4/48 |
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| author | Karina González-García Jovito Cesar Santos-Álvarez Juan Manuel Velázquez-Enríquez Cecilia Zertuche-Martínez Edilburga Reyes-Jiménez Rafael Baltiérrez-Hoyos Verónica Rocío Vásquez-Garzón |
| author_facet | Karina González-García Jovito Cesar Santos-Álvarez Juan Manuel Velázquez-Enríquez Cecilia Zertuche-Martínez Edilburga Reyes-Jiménez Rafael Baltiérrez-Hoyos Verónica Rocío Vásquez-Garzón |
| author_sort | Karina González-García |
| collection | DOAJ |
| description | Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, disabling disorder of unknown etiology, poor prognosis, and limited therapeutic options. Previously, 3′5-dimaleamylbenzoic acid (3′5-DMBA) was shown to exert resolving effects in IPF, offering a promising alternative for treating this disease; however, the molecular mechanisms associated with this effect have not been explored. Objetive: We evaluated the potential antifibrotic mechanisms of 3′5-DMBA by network pharmacology (NP) and molecular docking (MD). Methods: 3′5-DMBA-associated targets were identified by screening in SwissTargetPrediction. IPF-associated targets were identified using lung tissue meta-analysis and public databases. Common targets were identified, and a protein–protein interaction (PPI) network was constructed; we ranked the proteins in the PPI network by topological analysis. MD validated the binding of 3′5-DMBA to the main therapeutic targets. Results: A total of 57 common targets were identified between 3′5-DMBA and IPF; caspase 8, 9, 3, and 7; myeloid leukemia-induced cell differentiation protein Mcl-1; and poly [ADP-ribose] polymerase 1 are primary targets regulating PPI networks. Functional analysis revealed that the common targets are involved in the pathological features of tissue fibrosis and primarily in the apoptotic process. MD revealed favorable interaction energies among the three main targets regulating PPI networks. Conclusions: NP results suggest that the antifibrotic effect of 3′5-DMBA is due to its regulation of the pathological features of IPF, mainly by modulating signaling pathways leading to apoptosis, suggesting its therapeutic potential to treat this disease. |
| format | Article |
| id | doaj-art-2ea42d65b637499a851982911b3feef7 |
| institution | DOAJ |
| issn | 2813-2998 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Drugs and Drug Candidates |
| spelling | doaj-art-2ea42d65b637499a851982911b3feef72025-08-20T02:56:06ZengMDPI AGDrugs and Drug Candidates2813-29982024-12-013486087810.3390/ddc3040048Evaluation of Antifibrotic Mechanisms of 3′5-Dimaleamylbenzoic Acid on Idiopathic Pulmonary Fibrosis: A Network Pharmacology and Molecular Docking AnalysisKarina González-García0Jovito Cesar Santos-Álvarez1Juan Manuel Velázquez-Enríquez2Cecilia Zertuche-Martínez3Edilburga Reyes-Jiménez4Rafael Baltiérrez-Hoyos5Verónica Rocío Vásquez-Garzón6Laboratory of Fibrosis and Cancer, Faculty of Medicine and Surgery, Autonomous University “Benito Juárez” of Oaxaca, Oaxaca de Juarez 68120, Oaxaca, MexicoLaboratory of Fibrosis and Cancer, Faculty of Medicine and Surgery, Autonomous University “Benito Juárez” of Oaxaca, Oaxaca de Juarez 68120, Oaxaca, MexicoLaboratory of Fibrosis and Cancer, Faculty of Medicine and Surgery, Autonomous University “Benito Juárez” of Oaxaca, Oaxaca de Juarez 68120, Oaxaca, MexicoLaboratory of Fibrosis and Cancer, Faculty of Medicine and Surgery, Autonomous University “Benito Juárez” of Oaxaca, Oaxaca de Juarez 68120, Oaxaca, MexicoLaboratory of Fibrosis and Cancer, Faculty of Medicine and Surgery, Autonomous University “Benito Juárez” of Oaxaca, Oaxaca de Juarez 68120, Oaxaca, MexicoCONAHCYT- Faculty of Medicine and Surgery, Autonomous University “Benito Juárez” of Oaxaca, Oaxaca de Juarez 68120, Oaxaca, MexicoCONAHCYT- Faculty of Medicine and Surgery, Autonomous University “Benito Juárez” of Oaxaca, Oaxaca de Juarez 68120, Oaxaca, MexicoBackground: Idiopathic pulmonary fibrosis (IPF) is a chronic, disabling disorder of unknown etiology, poor prognosis, and limited therapeutic options. Previously, 3′5-dimaleamylbenzoic acid (3′5-DMBA) was shown to exert resolving effects in IPF, offering a promising alternative for treating this disease; however, the molecular mechanisms associated with this effect have not been explored. Objetive: We evaluated the potential antifibrotic mechanisms of 3′5-DMBA by network pharmacology (NP) and molecular docking (MD). Methods: 3′5-DMBA-associated targets were identified by screening in SwissTargetPrediction. IPF-associated targets were identified using lung tissue meta-analysis and public databases. Common targets were identified, and a protein–protein interaction (PPI) network was constructed; we ranked the proteins in the PPI network by topological analysis. MD validated the binding of 3′5-DMBA to the main therapeutic targets. Results: A total of 57 common targets were identified between 3′5-DMBA and IPF; caspase 8, 9, 3, and 7; myeloid leukemia-induced cell differentiation protein Mcl-1; and poly [ADP-ribose] polymerase 1 are primary targets regulating PPI networks. Functional analysis revealed that the common targets are involved in the pathological features of tissue fibrosis and primarily in the apoptotic process. MD revealed favorable interaction energies among the three main targets regulating PPI networks. Conclusions: NP results suggest that the antifibrotic effect of 3′5-DMBA is due to its regulation of the pathological features of IPF, mainly by modulating signaling pathways leading to apoptosis, suggesting its therapeutic potential to treat this disease.https://www.mdpi.com/2813-2998/3/4/48apoptosismaleimidepro-oxidantsPI3K-AktHIF-1αfibroblasts |
| spellingShingle | Karina González-García Jovito Cesar Santos-Álvarez Juan Manuel Velázquez-Enríquez Cecilia Zertuche-Martínez Edilburga Reyes-Jiménez Rafael Baltiérrez-Hoyos Verónica Rocío Vásquez-Garzón Evaluation of Antifibrotic Mechanisms of 3′5-Dimaleamylbenzoic Acid on Idiopathic Pulmonary Fibrosis: A Network Pharmacology and Molecular Docking Analysis Drugs and Drug Candidates apoptosis maleimide pro-oxidants PI3K-Akt HIF-1α fibroblasts |
| title | Evaluation of Antifibrotic Mechanisms of 3′5-Dimaleamylbenzoic Acid on Idiopathic Pulmonary Fibrosis: A Network Pharmacology and Molecular Docking Analysis |
| title_full | Evaluation of Antifibrotic Mechanisms of 3′5-Dimaleamylbenzoic Acid on Idiopathic Pulmonary Fibrosis: A Network Pharmacology and Molecular Docking Analysis |
| title_fullStr | Evaluation of Antifibrotic Mechanisms of 3′5-Dimaleamylbenzoic Acid on Idiopathic Pulmonary Fibrosis: A Network Pharmacology and Molecular Docking Analysis |
| title_full_unstemmed | Evaluation of Antifibrotic Mechanisms of 3′5-Dimaleamylbenzoic Acid on Idiopathic Pulmonary Fibrosis: A Network Pharmacology and Molecular Docking Analysis |
| title_short | Evaluation of Antifibrotic Mechanisms of 3′5-Dimaleamylbenzoic Acid on Idiopathic Pulmonary Fibrosis: A Network Pharmacology and Molecular Docking Analysis |
| title_sort | evaluation of antifibrotic mechanisms of 3 5 dimaleamylbenzoic acid on idiopathic pulmonary fibrosis a network pharmacology and molecular docking analysis |
| topic | apoptosis maleimide pro-oxidants PI3K-Akt HIF-1α fibroblasts |
| url | https://www.mdpi.com/2813-2998/3/4/48 |
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