From Myricetin to the Discovery of Novel Natural Human ENPP1 Inhibitors: A Virtual Screening,Molecular Docking,Molecular Dynamics Simulation,and MM/GBSA Study |
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Authors: | Shaohan Song Zhiyu Shao |
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Affiliation: | 1.Shanghai Foreign Language School Affiliated to Shanghai International Studies University, Shanghai 200083, China;2.College of Chemistry and Chemical Engineering, Donghua University, Shanghai 201620, China |
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Abstract: | It was recently revealed that naturally occurring myricetin can inhibit ectonucleotidase ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which, in turn, can treat ischemic cardiac injury. However, due to myricetin’s poor druggability, its further developments are relatively limited, which necessitates the discovery of novel ENPP1-inhibiting myricetin analogs as alternatives. In this study, the binding model of myricetin with ENPP1 was elucidated by molecular docking and molecular dynamics studies. Subsequently, virtual screening on the self-developed flavonoid natural product database (FNPD), led to the identification of two flavonoid glycosides (Cas No: 1397173-50-0 and 1169835-58-8), as potential ENPP1 inhibitors. Docking scores and MM/GBSA binding energies predicted that they might have higher inhibitory effects than myricetin. This study provides a strong foundation for the future development of ischemic cardiac injury drugs. |
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Keywords: | ENPP1 inhibitor virtual screening biological evaluation myricetin molecular docking molecular dynamics |
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