Naturally occurring quercetin and myricetin as potent inhibitors for human ectonucleotide pyrophosphatase/phosphodiesterase 1
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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-01-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-50590-7 |
| _version_ | 1797363474087542784 |
|---|---|
| author | Peeradon Duangiad Bodee Nutho Thawatchai Chaijarasphong Noppawan Phumala Morales Thunyarat Pongtharangkul Itaru Hamachi Akio Ojida Jirarut Wongkongkatep |
| author_facet | Peeradon Duangiad Bodee Nutho Thawatchai Chaijarasphong Noppawan Phumala Morales Thunyarat Pongtharangkul Itaru Hamachi Akio Ojida Jirarut Wongkongkatep |
| author_sort | Peeradon Duangiad |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T16:20:54Z |
| format | Article |
| id | doaj.art-e4d7ead469c549519a46148e1233f6d0 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-08T16:20:54Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-e4d7ead469c549519a46148e1233f6d02024-01-07T12:21:55ZengNature PortfolioScientific Reports2045-23222024-01-0114111310.1038/s41598-023-50590-7Naturally occurring quercetin and myricetin as potent inhibitors for human ectonucleotide pyrophosphatase/phosphodiesterase 1Peeradon Duangiad0Bodee Nutho1Thawatchai Chaijarasphong2Noppawan Phumala Morales3Thunyarat Pongtharangkul4Itaru Hamachi5Akio Ojida6Jirarut Wongkongkatep7Department of Biotechnology, Faculty of Science, Mahidol UniversityDepartment of Pharmacology, Faculty of Science, Mahidol UniversityDepartment of Biotechnology, Faculty of Science, Mahidol UniversityDepartment of Pharmacology, Faculty of Science, Mahidol UniversityDepartment of Biotechnology, Faculty of Science, Mahidol UniversityDepartment of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto UniversityGraduate School of Pharmaceutical Sciences, Kyushu UniversityDepartment of Biotechnology, Faculty of Science, Mahidol UniversityAbstract 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.https://doi.org/10.1038/s41598-023-50590-7 |
| spellingShingle | Peeradon Duangiad Bodee Nutho Thawatchai Chaijarasphong Noppawan Phumala Morales Thunyarat Pongtharangkul Itaru Hamachi Akio Ojida Jirarut Wongkongkatep Naturally occurring quercetin and myricetin as potent inhibitors for human ectonucleotide pyrophosphatase/phosphodiesterase 1 Scientific Reports |
| title | Naturally occurring quercetin and myricetin as potent inhibitors for human ectonucleotide pyrophosphatase/phosphodiesterase 1 |
| title_full | Naturally occurring quercetin and myricetin as potent inhibitors for human ectonucleotide pyrophosphatase/phosphodiesterase 1 |
| title_fullStr | Naturally occurring quercetin and myricetin as potent inhibitors for human ectonucleotide pyrophosphatase/phosphodiesterase 1 |
| title_full_unstemmed | Naturally occurring quercetin and myricetin as potent inhibitors for human ectonucleotide pyrophosphatase/phosphodiesterase 1 |
| title_short | Naturally occurring quercetin and myricetin as potent inhibitors for human ectonucleotide pyrophosphatase/phosphodiesterase 1 |
| title_sort | naturally occurring quercetin and myricetin as potent inhibitors for human ectonucleotide pyrophosphatase phosphodiesterase 1 |
| url | https://doi.org/10.1038/s41598-023-50590-7 |
| work_keys_str_mv | AT peeradonduangiad naturallyoccurringquercetinandmyricetinaspotentinhibitorsforhumanectonucleotidepyrophosphatasephosphodiesterase1 AT bodeenutho naturallyoccurringquercetinandmyricetinaspotentinhibitorsforhumanectonucleotidepyrophosphatasephosphodiesterase1 AT thawatchaichaijarasphong naturallyoccurringquercetinandmyricetinaspotentinhibitorsforhumanectonucleotidepyrophosphatasephosphodiesterase1 AT noppawanphumalamorales naturallyoccurringquercetinandmyricetinaspotentinhibitorsforhumanectonucleotidepyrophosphatasephosphodiesterase1 AT thunyaratpongtharangkul naturallyoccurringquercetinandmyricetinaspotentinhibitorsforhumanectonucleotidepyrophosphatasephosphodiesterase1 AT itaruhamachi naturallyoccurringquercetinandmyricetinaspotentinhibitorsforhumanectonucleotidepyrophosphatasephosphodiesterase1 AT akioojida naturallyoccurringquercetinandmyricetinaspotentinhibitorsforhumanectonucleotidepyrophosphatasephosphodiesterase1 AT jirarutwongkongkatep naturallyoccurringquercetinandmyricetinaspotentinhibitorsforhumanectonucleotidepyrophosphatasephosphodiesterase1 |