Naturally occurring quercetin and myricetin as potent inhibitors for human ectonucleotide pyrophosphatase/phosphodiesterase 1
Issued Date
2024-12-01
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-85181220373
Pubmed ID
38167594
Journal Title
Scientific Reports
Volume
14
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scientific Reports Vol.14 No.1 (2024)
Suggested Citation
Duangiad P., Nutho B., Chaijarasphong T., Morales N.P., Pongtharangkul T., Hamachi I., Ojida A., Wongkongkatep J. Naturally occurring quercetin and myricetin as potent inhibitors for human ectonucleotide pyrophosphatase/phosphodiesterase 1. Scientific Reports Vol.14 No.1 (2024). doi:10.1038/s41598-023-50590-7 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/95754
Title
Naturally occurring quercetin and myricetin as potent inhibitors for human ectonucleotide pyrophosphatase/phosphodiesterase 1
Corresponding Author(s)
Other Contributor(s)
Abstract
Ecto-nucleotide pyrophosphatases/phosphodiesterases 1 (ENPP1) is a key enzyme in purinergic signaling pathways responsible for cell-to-cell communications and regulation of several fundamental pathophysiological processes. In this study, Kyoto Green, a rapid chemical sensor of pyrophosphate, was employed to screen for effective ENPP1 inhibitors among five representative flavonoids (quercetin, myricetin, morin, kaempferol, and quercetin-3-glucoside), five nucleosides (adenosine, guanosine, inosine, uridine, and cytidine), and five deoxynucleosides (2′- and 3′-deoxyadenosine, 2′-deoxyguanosine, 2′-deoxyinosine, and 2′-deoxyuridine). Conventional colorimetric, fluorescence, and bioluminescence assays revealed that ENPP1 was effectively inhibited by quercetin (K i ~ 4 nM) and myricetin (K i ~ 32 nM) when ATP was used as a substrate at pH 7.4. In silico analysis indicated that the presence of a chromone scaffold, particularly one containing a hydroxyl group at the 3′ position on the B ring, may promote binding to the active site pocket of ENPP1 and enhance inhibition. This study demonstrated that the naturally derived quercetin and myricetin could effectively inhibit ENPP1 enzymatic activity and may offer health benefits in arthritis management.