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• W4286435992 endingPage "114621" @default.
• W4286435992 startingPage "114621" @default.
• W4286435992 abstract "Although multivalent glucosidase inhibitors based on iminosugars have shown enhanced inhibition activity, an effective way to improve their hypoglycemic effect in vivo, is still in infancy and needs further development. In this paper, PBI-5DNJ and PBI-6DNJ, with three or four DNJ moieties respectively conjugated at the bay position were synthesized. PBI-6DNJ evidenced stronger π-π stacking interactions and, when self-assembled, a smaller size than that of PBI-5DNJ. It was found that PBI-6DNJ exhibited superior α-glucosidases (from mice) inhibition activity (Ki = 0.14 ± 0.007 μM) in vitro than that (Ki = 0.31 ± 0.01) of PBI-5DNJ and in vivo hypoglycemic effects in mice models. PBI-6DNJ possessed good hypoglycemic effects with the percentages of PBG levels of 40.40 ± 3.33% and 39.23 ± 4.84% at a dose of 2.0 mg/kg after 15 min and 30 min of administration, respectively. In terms of measuring percentage decrease of PBG level per DNJ unit, PBI-6DNJ displayed a 2.1-fold enhancement than miglitol, demonstrating a consistency between in vitro and in vivo experiments. This paves the way to the connection between in vivo hypoglycemic potency and in vitro glucosidase inhibition assay, leading to reliable and simplified assessment of hypoglycemic potency determination, and opening a basic understanding of the design of multivalent glucosidase inhibitors." @default.
• W4286435992 created "2022-07-22" @default.
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• W4286435992 date "2022-11-01" @default.
• W4286435992 modified "2023-09-27" @default.
• W4286435992 title "Multivalent glucosidase inhibitors based on perylene bisimide and iminosugar conjugates" @default.
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• W4286435992 doi "https://doi.org/10.1016/j.ejmech.2022.114621" @default.
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