Status : Verified
| Personal Name | Macalalad, Mark Andrian B. |
|---|---|
| Resource Title | In-silico screening and identification of antidiabetic inhibitors sourced from phytochemicals of Philippine plants against four protein targets of diabetes |
| Date Issued | June 2023 |
| Abstract | 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 getting more costly, and there is also the risk of developing the combined side effects of each drug. Thus, identifying a multi-target drug, either plant-based or semi-synthetic, may be the best strategy to improve treatment efficacy. This study sees the potential of 3,083 Philippine phytochemicals as a source of natural inhibitors against four targets of diabetes: Protein-tyrosine phosphatase 1B (PTP1B), Dipeptidyl peptidase-4 (DPP-4), Sodium-glucose co-transporter 2 (SGLT-2), and Fructose 1,6-biphosphatase (FBPase). A wide array of computer-aided drug discovery techniques were employed to carry out the virtual screening process: ADMET profiling revealed 373 molecules with excellent bioavailability and toxicity properties; DFT optimization predicted their most accurate 3D structures; consensus docking identified the ten highest-scoring ligands per protein comparable to reference compounds' scores; molecular dynamics simulation elucidated the stability of the protein-ligand complexes trough RMSD, RMSF, and H-bond diagram analysis; and MM/PBSA energy calculations determined the binding affinity of the compounds against the four receptors and the key residues integral to binding. 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 (Eclipta prostata, Agave sisalana, Piper aduncum, Curculigo orchioides, Luffa cylindrica, Moringa oleifera, Alium cepa, and Helianthus annuus). It is recommended to investigate |
| Degree Course | PhD Chemical Engineering |
| Language | English |
| Keyword | natural compounds; MM/PBSA; MD simulations; molecular docking; ADMET; FBPase; SGLT-2; DPP-4; PTP1B; phytochemicals; diabetes |
| Material Type | Thesis/Dissertation |
Preliminary Pages
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Category : P - Author wishes to publish the work personally.
Access Permission : Limited Access