In Silico Screening and Identification of Antidiabetic Inhibitors Sourced from Phytochemicals of Philippine Plants against Four Protein Targets of Diabetes (PTP1B, DPP-4, SGLT-2, and FBPase)
Current oral medications for type 2 diabetes target a single main physiological mechanism. They either activate or inhibit receptors to enhance insulin sensitivity, increase insulin secretion, inhibit glucose absorption, or inhibit glucose production. In advanced stages, combination therapy may be r...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/28/14/5301 |
| _version_ | 1797588090216251392 |
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| author | Mark Andrian B. Macalalad Arthur A. Gonzales |
| author_facet | Mark Andrian B. Macalalad Arthur A. Gonzales |
| author_sort | Mark Andrian B. Macalalad |
| collection | DOAJ |
| description | Current oral medications for type 2 diabetes target a single main physiological mechanism. They either activate or inhibit receptors to enhance insulin sensitivity, increase insulin secretion, inhibit glucose absorption, or inhibit glucose production. In advanced stages, combination therapy may be required because of the limited efficacy of single-target drugs; however, medications are becoming more costly, and there is also the risk of developing the combined side effects of each drug. Thus, identifying a multi-target drug may be the best strategy to improve treatment efficacy. This study sees the potential of 2657 Filipino phytochemicals as a source of natural inhibitors against four targets of diabetes: PTP1B, DPP-4, SGLT-2, and FBPase. Different computer-aided drug discovery techniques, including ADMET profiling, DFT optimization, molecular docking, MD simulations, and MM/PBSA energy calculations, were employed to elucidate the stability and determine the binding affinity of the candidate ligands. Through in silico methods, we have identified seven potential natural inhibitors against PTP1B, DPP-4, and FBPase, and ten against SGLT-2. Eight plants containing at least one natural inhibitor of each protein target were also identified. It is recommended to further investigate the plants’ potential to be transformed into a safe and scientifically validated multi-target drug for diabetes therapies. |
| first_indexed | 2024-03-11T00:47:52Z |
| format | Article |
| id | doaj.art-5b84b95138ee40b8ba7e8df00f81b3c9 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T00:47:52Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-5b84b95138ee40b8ba7e8df00f81b3c92023-11-18T20:40:05ZengMDPI AGMolecules1420-30492023-07-012814530110.3390/molecules28145301In Silico Screening and Identification of Antidiabetic Inhibitors Sourced from Phytochemicals of Philippine Plants against Four Protein Targets of Diabetes (PTP1B, DPP-4, SGLT-2, and FBPase)Mark Andrian B. Macalalad0Arthur A. Gonzales1Department of Chemical Engineering, University of the Philippines Diliman, Quezon City 1101, Metro Manila, PhilippinesDepartment of Chemical Engineering, University of the Philippines Diliman, Quezon City 1101, Metro Manila, PhilippinesCurrent oral medications for type 2 diabetes target a single main physiological mechanism. They either activate or inhibit receptors to enhance insulin sensitivity, increase insulin secretion, inhibit glucose absorption, or inhibit glucose production. In advanced stages, combination therapy may be required because of the limited efficacy of single-target drugs; however, medications are becoming more costly, and there is also the risk of developing the combined side effects of each drug. Thus, identifying a multi-target drug may be the best strategy to improve treatment efficacy. This study sees the potential of 2657 Filipino phytochemicals as a source of natural inhibitors against four targets of diabetes: PTP1B, DPP-4, SGLT-2, and FBPase. Different computer-aided drug discovery techniques, including ADMET profiling, DFT optimization, molecular docking, MD simulations, and MM/PBSA energy calculations, were employed to elucidate the stability and determine the binding affinity of the candidate ligands. Through in silico methods, we have identified seven potential natural inhibitors against PTP1B, DPP-4, and FBPase, and ten against SGLT-2. Eight plants containing at least one natural inhibitor of each protein target were also identified. It is recommended to further investigate the plants’ potential to be transformed into a safe and scientifically validated multi-target drug for diabetes therapies.https://www.mdpi.com/1420-3049/28/14/5301diabetesphytochemicalsnatural compoundsPTP1BDPP-4SGLT-2 |
| spellingShingle | Mark Andrian B. Macalalad Arthur A. Gonzales In Silico Screening and Identification of Antidiabetic Inhibitors Sourced from Phytochemicals of Philippine Plants against Four Protein Targets of Diabetes (PTP1B, DPP-4, SGLT-2, and FBPase) Molecules diabetes phytochemicals natural compounds PTP1B DPP-4 SGLT-2 |
| title | In Silico Screening and Identification of Antidiabetic Inhibitors Sourced from Phytochemicals of Philippine Plants against Four Protein Targets of Diabetes (PTP1B, DPP-4, SGLT-2, and FBPase) |
| title_full | In Silico Screening and Identification of Antidiabetic Inhibitors Sourced from Phytochemicals of Philippine Plants against Four Protein Targets of Diabetes (PTP1B, DPP-4, SGLT-2, and FBPase) |
| title_fullStr | In Silico Screening and Identification of Antidiabetic Inhibitors Sourced from Phytochemicals of Philippine Plants against Four Protein Targets of Diabetes (PTP1B, DPP-4, SGLT-2, and FBPase) |
| title_full_unstemmed | In Silico Screening and Identification of Antidiabetic Inhibitors Sourced from Phytochemicals of Philippine Plants against Four Protein Targets of Diabetes (PTP1B, DPP-4, SGLT-2, and FBPase) |
| title_short | In Silico Screening and Identification of Antidiabetic Inhibitors Sourced from Phytochemicals of Philippine Plants against Four Protein Targets of Diabetes (PTP1B, DPP-4, SGLT-2, and FBPase) |
| title_sort | in silico screening and identification of antidiabetic inhibitors sourced from phytochemicals of philippine plants against four protein targets of diabetes ptp1b dpp 4 sglt 2 and fbpase |
| topic | diabetes phytochemicals natural compounds PTP1B DPP-4 SGLT-2 |
| url | https://www.mdpi.com/1420-3049/28/14/5301 |
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