α-Glucosidase inhibition of lactone intermediates of the iminosugar deoxynojirimycin
α-Glycosidase enzymes hydrolyse α-glycosidic linkages and are involved in bodily processes such as the catabolism of glycans, intestinal digestion, and the degradation of glycoproteins. Various types of diseases which are caused by the failure of this enzyme to function prope...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Penerbit UTM Press
2019
|
| _version_ | 1797112582209798144 |
|---|---|
| author | Wai Haan, Y Al-Bajalan, H Eukun Sage, E Elangovan, D Liana Mat Yajit, N Maisarah Sarizan, N Zitzmann, N Kiappes, J Aishah Hasbullah, S Hadiani Ismail, N Mohamed Mackeen, M |
| author_facet | Wai Haan, Y Al-Bajalan, H Eukun Sage, E Elangovan, D Liana Mat Yajit, N Maisarah Sarizan, N Zitzmann, N Kiappes, J Aishah Hasbullah, S Hadiani Ismail, N Mohamed Mackeen, M |
| author_sort | Wai Haan, Y |
| collection | OXFORD |
| description | α-Glycosidase enzymes hydrolyse α-glycosidic linkages and are involved in bodily processes such as the catabolism of glycans, intestinal digestion, and the degradation of glycoproteins. Various types of diseases which are caused by the failure of this enzyme to function properly can be treated through enzyme inhibition. The hydroxyethyl derivative of DNJ (Miglitol) is a clinical drug for the treatment of type 2 diabetes. Although the iminosugar D-deoxynojirimisin (D-DNJ) is an excellent micromolar glycosidase inhibitor, the α-glucosidase inhibition activity of D-DNJ lactone intermediates has yet to be reported. Therefore, the scalable synthesis of the D-DNJ intermediates 1,2-O-isopropylidene-α-D-glucurono-3,6-lactone (2), 1,2-O-isopropylidene-β-L-idurono-3,6-lactone (3) and 5-azido-5-deoxy-1,2-O-isopropylidene-α-D-glucurono-3,6-lactone (4) was carried out using D-glucuronolactone (1) as the starting material based on the method reported by Best et al. 2010 with some modification and subsequently, evaluated for anti-α-glucosidase activity. All products were characterised and identified by HPLC-ELSD, mass spectrometry (DI-ESI-MS) and NMR spectroscopy (via comparison of 1D 1H and 13C data with previously reported values). The inhibitory activity of compounds 1-4 towards α-glucosidase from Saccharomyces cerevisiae was evaluated using the p-nitrophenyl α-D-glucopyranoside substrate. Compound 3 showed 29.5% inhibition followed by 2 (21.4%), 1 (15.8%) and 4 (15.7%) compared to the positive control, quercetin (72.7%). |
| first_indexed | 2024-03-07T08:27:39Z |
| format | Journal article |
| id | oxford-uuid:70904b45-9da2-4d0b-8986-c39b9485f51b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:27:39Z |
| publishDate | 2019 |
| publisher | Penerbit UTM Press |
| record_format | dspace |
| spelling | oxford-uuid:70904b45-9da2-4d0b-8986-c39b9485f51b2024-02-22T10:03:39Zα-Glucosidase inhibition of lactone intermediates of the iminosugar deoxynojirimycinJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:70904b45-9da2-4d0b-8986-c39b9485f51bEnglishSymplectic Elements at OxfordPenerbit UTM Press2019Wai Haan, YAl-Bajalan, HEukun Sage, EElangovan, DLiana Mat Yajit, NMaisarah Sarizan, NZitzmann, NKiappes, JAishah Hasbullah, SHadiani Ismail, NMohamed Mackeen, Mα-Glycosidase enzymes hydrolyse α-glycosidic linkages and are involved in bodily processes such as the catabolism of glycans, intestinal digestion, and the degradation of glycoproteins. Various types of diseases which are caused by the failure of this enzyme to function properly can be treated through enzyme inhibition. The hydroxyethyl derivative of DNJ (Miglitol) is a clinical drug for the treatment of type 2 diabetes. Although the iminosugar D-deoxynojirimisin (D-DNJ) is an excellent micromolar glycosidase inhibitor, the α-glucosidase inhibition activity of D-DNJ lactone intermediates has yet to be reported. Therefore, the scalable synthesis of the D-DNJ intermediates 1,2-O-isopropylidene-α-D-glucurono-3,6-lactone (2), 1,2-O-isopropylidene-β-L-idurono-3,6-lactone (3) and 5-azido-5-deoxy-1,2-O-isopropylidene-α-D-glucurono-3,6-lactone (4) was carried out using D-glucuronolactone (1) as the starting material based on the method reported by Best et al. 2010 with some modification and subsequently, evaluated for anti-α-glucosidase activity. All products were characterised and identified by HPLC-ELSD, mass spectrometry (DI-ESI-MS) and NMR spectroscopy (via comparison of 1D 1H and 13C data with previously reported values). The inhibitory activity of compounds 1-4 towards α-glucosidase from Saccharomyces cerevisiae was evaluated using the p-nitrophenyl α-D-glucopyranoside substrate. Compound 3 showed 29.5% inhibition followed by 2 (21.4%), 1 (15.8%) and 4 (15.7%) compared to the positive control, quercetin (72.7%). |
| spellingShingle | Wai Haan, Y Al-Bajalan, H Eukun Sage, E Elangovan, D Liana Mat Yajit, N Maisarah Sarizan, N Zitzmann, N Kiappes, J Aishah Hasbullah, S Hadiani Ismail, N Mohamed Mackeen, M α-Glucosidase inhibition of lactone intermediates of the iminosugar deoxynojirimycin |
| title | α-Glucosidase inhibition of lactone intermediates of the iminosugar deoxynojirimycin |
| title_full | α-Glucosidase inhibition of lactone intermediates of the iminosugar deoxynojirimycin |
| title_fullStr | α-Glucosidase inhibition of lactone intermediates of the iminosugar deoxynojirimycin |
| title_full_unstemmed | α-Glucosidase inhibition of lactone intermediates of the iminosugar deoxynojirimycin |
| title_short | α-Glucosidase inhibition of lactone intermediates of the iminosugar deoxynojirimycin |
| title_sort | α glucosidase inhibition of lactone intermediates of the iminosugar deoxynojirimycin |
| work_keys_str_mv | AT waihaany aglucosidaseinhibitionoflactoneintermediatesoftheiminosugardeoxynojirimycin AT albajalanh aglucosidaseinhibitionoflactoneintermediatesoftheiminosugardeoxynojirimycin AT eukunsagee aglucosidaseinhibitionoflactoneintermediatesoftheiminosugardeoxynojirimycin AT elangovand aglucosidaseinhibitionoflactoneintermediatesoftheiminosugardeoxynojirimycin AT lianamatyajitn aglucosidaseinhibitionoflactoneintermediatesoftheiminosugardeoxynojirimycin AT maisarahsarizann aglucosidaseinhibitionoflactoneintermediatesoftheiminosugardeoxynojirimycin AT zitzmannn aglucosidaseinhibitionoflactoneintermediatesoftheiminosugardeoxynojirimycin AT kiappesj aglucosidaseinhibitionoflactoneintermediatesoftheiminosugardeoxynojirimycin AT aishahhasbullahs aglucosidaseinhibitionoflactoneintermediatesoftheiminosugardeoxynojirimycin AT hadianiismailn aglucosidaseinhibitionoflactoneintermediatesoftheiminosugardeoxynojirimycin AT mohamedmackeenm aglucosidaseinhibitionoflactoneintermediatesoftheiminosugardeoxynojirimycin |