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)

被引:12
作者
Macalalad, Mark Andrian B. [1 ]
Gonzales III, Arthur A. A. [1 ]
机构
[1] Univ Philippines Diliman, Dept Chem Engn, Quezon City 1101, Metro Manila, Philippines
来源
MOLECULES | 2023年 / 28卷 / 14期
关键词
diabetes; phytochemicals; natural compounds; PTP1B; DPP-4; SGLT-2; FBPase; ADMET; molecular docking; MD simulations; MM; PBSA; CURCULIGO-ORCHIOIDES; NATURAL-PRODUCTS; AGAVE-SISALANA; PIPER; FRUCTOSE-1,6-BISPHOSPHATASE; DIHYDROCHALCONES; OPTIMIZATION; DOCKING; GROMACS; CHARMM;
D O I
10.3390/molecules28145301
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
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页数:33
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共 89 条
  • [41] Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors: A Review of Their Basic and Clinical Pharmacology
    Kalra, Sanjay
    [J]. DIABETES THERAPY, 2014, 5 (02) : 355 - 366
  • [42] Kasina S. V. S. K., 2021, StatPearls
  • [43] Fructose-1,6-bisphosphatase inhibitors: A new valid approach for management of type 2 diabetes mellitus
    Kaur, Ramandeep
    Dahiya, Lalita
    Kumar, Manoj
    [J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2017, 141 : 473 - 505
  • [44] PubChem Substance and Compound databases
    Kim, Sunghwan
    Thiessen, Paul A.
    Bolton, Evan E.
    Chen, Jie
    Fu, Gang
    Gindulyte, Asta
    Han, Lianyi
    He, Jane
    He, Siqian
    Shoemaker, Benjamin A.
    Wang, Jiyao
    Yu, Bo
    Zhang, Jian
    Bryant, Stephen H.
    [J]. NUCLEIC ACIDS RESEARCH, 2016, 44 (D1) : D1202 - D1213
  • [45] Inhibitor selectivity in the clinical application of dipeptidyl peptidase-4 inhibition
    Kirby, Mark
    Yu, Denise M. T.
    O'Connor, Stephen P.
    Gorrell, Mark D.
    [J]. CLINICAL SCIENCE, 2010, 118 (1-2) : 31 - 41
  • [46] Kirtikar K., 1975, Indian Medicinal Plants, P1465
  • [47] New Drugs for Type 2 Diabetes Mellitus What is their Place in Therapy?
    Krentz, Andrew J.
    Patel, Mayank B.
    Bailey, Clifford J.
    [J]. DRUGS, 2008, 68 (15) : 2131 - 2162
  • [48] g_mmpbsa-A GROMACS Tool for High-Throughput MM-PBSA Calculations
    Kumari, Rashmi
    Kumar, Rajendra
    Lynn, Andrew
    [J]. JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2014, 54 (07) : 1951 - 1962
  • [49] Understanding glycaemic control and current approaches for screening antidiabetic natural products from evidence-based medicinal plants
    Lankatillake, Chintha
    Huynh, Tien
    Dias, Daniel A.
    [J]. PLANT METHODS, 2019, 15 (01)
  • [50] Moringa oleifera Seeds and Oil: Characteristics and Uses for Human Health
    Leone, Alessandro
    Spada, Alberto
    Battezzati, Alberto
    Schiraldi, Alberto
    Aristil, Junior
    Bertoli, Simona
    [J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2016, 17 (12):