Characterization of Plant-Derived Natural Inhibitors of Dipeptidyl Peptidase-4 as Potential Antidiabetic Agents: A Computational Study
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Published:2024-04-01
Issue:4
Volume:16
Page:483
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ISSN:1999-4923
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Container-title:Pharmaceutics
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language:en
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Short-container-title:Pharmaceutics
Author:
Hossain Alomgir1, Rahman Md Ekhtiar1, Faruqe Md Omar2ORCID, Saif Ahmed3ORCID, Suhi Suzzada4, Zaman Rashed1ORCID, Hirad Abdurahman Hajinur5, Matin Mohammad Nurul16ORCID, Rabbee Muhammad Fazle6, Baek Kwang-Hyun6ORCID
Affiliation:
1. Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi 6205, Bangladesh 2. Department of Computer Science and Engineering, University of Rajshahi, Rajshahi 6205, Bangladesh 3. Department of Pharmacy, University of Rajshahi, Rajshahi 6205, Bangladesh 4. Department of Zoology, University of Rajshahi, Rajshahi 6205, Bangladesh 5. Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia 6. Department of Biotechnology, Yeungnam University, Gyeongsan 38541, Gyeongsangbuk-do, Republic of Korea
Abstract
Diabetes, characterized by elevated blood sugar levels, poses significant health and economic risks, correlating with complications like cardiovascular disease, kidney failure, and blindness. Dipeptidyl peptidase-4 (DPP-4), also referred to as T-cell activation antigen CD26 (EC 3.4.14.5.), plays a crucial role in glucose metabolism and immune function. Inhibiting DPP-4 was anticipated as a potential new therapy for diabetes. Therefore, identification of plant-based natural inhibitors of DPP-4 would help in eradicating diabetes worldwide. Here, for the identification of the potential natural inhibitors of DPP-4, we developed a phytochemicals library consisting of over 6000 phytochemicals detected in 81 medicinal plants that exhibited anti-diabetic potency. The library has been docked against the target proteins, where isorhamnetin, Benzyl 5-Amino-5-deoxy-2,3-O-isopropyl-alpha-D-mannofuranoside (DTXSID90724586), and 5-Oxo-7-[4-(trifluoromethyl) phenyl]-4H,6H,7H-[1,2]thiazolo[4,5-b]pyridine 3-carboxylic acid (CHEMBL3446108) showed binding affinities of −8.5, −8.3, and −8.3 kcal/mol, respectively. These compounds exhibiting strong interactions with DPP-4 active sites (Glu205, Glu206, Tyr547, Trp629, Ser630, Tyr662, His740) were identified. ADME/T and bioactivity predictions affirmed their pharmacological safety. Density functional theory calculations assessed stability and reactivity, while molecular dynamics simulations demonstrated persistent stability. Analyzing parameters like RMSD, RG, RMSF, SASA, H-bonds, MM-PBSA, and FEL confirmed stable protein–ligand compound formation. Principal component analysis provided structural variation insights. Our findings suggest that those compounds might be possible candidates for developing novel inhibitors targeting DPP-4 for treating diabetes.
Funder
King Saud University, Riyadh, Saudi Arabia
Reference110 articles.
1. A modern overview on diabetes mellitus: A chronic endocrine disorder;Mukhtar;Eur. J. Biol.,2020 2. Chou, C.-Y., Hsu, D.-Y., and Chou, C.-H. (2023). Predicting the onset of diabetes with machine learning methods. J. Pers. Med., 13. 3. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045;Sun;Diabetes Res. Clin. Pract.,2022 4. Diabetes, cardiovascular disease and the microcirculation;Strain;Cardiovasc. Diabetol.,2018 5. Diabetes management in chronic kidney disease: A consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO);Khunti;Diabetes Care,2022
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