Fluorescence sensing and glycosidase inhibition effect of multivalent glycosidase inhibitors based on Naphthalimide-deoxynojirimycin conjugates

Wang, Guangyuan; Wei, Wen-Tong; Rong, Rui-Xue; Su, Shanshan; Yan, Dongxiao; Yin, Fang-Qian; Li, Xiaoliu; Wang, Ke-Rang

doi:10.1016/j.bioorg.2023.106373

Cited by 4 publications

(8 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To confirm the above hypothesis, the binding interactions of the assemblies of LP-4DNJ-6 with α-glucosidase (mice) were studied. As shown in Figure b, the fluorescence intensities of Nile red@ LP-4DNJ-6C markedly decreased from 3586 to 1746 with addition of different concentrations of α-glucosidase (mice), which equilibrated at a quenched ratio of 51% at the concentration of 3.0 × 10 –4 M. Furthermore, the binding constant was calculated as (5.68 ± 0.95) × 10 3 M –1 by a nonlinear least-squares cure-fitting method …”

Section: Resultsmentioning

confidence: 99%

“…As shown in Figure 4b, the fluorescence intensities of Nile red@LP-4DNJ-6C markedly decreased from 3586 to 1746 with addition of different concentrations of α-glucosidase (mice), which equilibrated at a quenched ratio of 51% at the concentration of 3.0 × 10 −4 M. Furthermore, the binding constant was calculated as (5.68 ± 0.95) × 10 3 M −1 by a nonlinear least-squares cure-fitting method. 36 Moreover, the binding interactions of DNJ and Miglitol with α-glucosidase (mice) were investigated by a competitive complexation method. As shown in Figure 4c,d addition of Miglitol, and the binding constant was calculated as (2.05 ± 0.77) × 10 2 M −1 , which was of the same magnitude as DNJ.…”

Section: Resultsmentioning

confidence: 99%

“…The IC 50 value was determined from the plot of % viability versus the doses. 36,58 4.8. Fluorescence Imaging in the Small Intestine.…”

Section: Dls and Tem Assaymentioning

confidence: 99%

“…35 These findings offer valuable insights for the future design of multivalent drugs targeting hypoglycemia. 36 However, future investigation is needed to confirm whether the self-assemblies retain sufficient stability to reach and bind to glycosidases in the small intestine.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Amphiphilic α-Peptoid-deoxynojirimycin Conjugate-based Multivalent Glycosidase Inhibitor for Hypoglycemic Effect and Fluorescence Imaging

Wang,

Yan,

Rong

et al. 2024

J. Med. Chem.

Self Cite

View full text Add to dashboard Cite

Multivalent glycosidase inhibitors based on 1-deoxynojirimycin derivatives against α-glucosidases have been rapidly developed. Nonetheless, the mechanism based on self-assembled multivalent glucosidase inhibitors in living systems needs to be further studied. It remains to be determined whether the self-assembly possesses sufficient stability to endure transit through the small intestine and subsequently bind to the glycosidases located therein. In this paper, two amphiphilic compounds, 1-deoxynojirimycin and α-peptoid conjugates (LP-4DNJ-3C and LP-4DNJ-6C), were designed. Their self-assembling behaviors, multivalent α-glucosidase inhibition effect, and fluorescence imaging on living organs were studied. LP-4DNJ-6C exhibited better multivalent α-glucosidase inhibition activities in vitro. Moreover, the self-assembly of LP-4DNJ-6C could effectively form a complex with Nile red. The complex showed fluorescence quenching effect upon binding with α-glucosidases and exhibited potent fluorescence imaging in the small intestine. This result suggests that a multivalent hypoglycemic effect achieved through self-assembly in the intestine is a viable approach, enabling the rational design of multivalent hypoglycemic drugs.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…The IC 50 value was determined from the plot of % viability versus the doses. 36,58 4.8. Fluorescence Imaging in the Small Intestine.…”

Section: Dls and Tem Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Amphiphilic α-Peptoid-deoxynojirimycin Conjugate-based Multivalent Glycosidase Inhibitor for Hypoglycemic Effect and Fluorescence Imaging

Wang,

Yan,

Rong

et al. 2024

J. Med. Chem.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Génisson dendrimers, calixarenes, cyclodextrins, cyclopeptides inter alia to generate multivalent glycosidases inhibitors. [7,[19][20][21][22][23][24][25][26] These studies have highlighted the importance of both platform topology and valency on the resulting biological activity. To graft the inhitope onto the surface of the multivalent scaffold, the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) remains the preferred reaction.…”

Section: Introductionmentioning

confidence: 99%

Phosphorus Dendrimers for Metal‐Free Ligation: Design of Multivalent Pharmacological Chaperones against Gaucher Disease

Tran

Borie-Guichot

Garcia

et al. 2023

Chemistry A European J

View full text Add to dashboard Cite

The first phosphorus dendrimers built on a cyclotriphosphazene core and decorated with six or twelve monofluorocyclooctyne units were prepared. A simple stirring allowed the grafting of N‐hexyl deoxynojirimycin inhitopes onto their surface by copper–free strain promoted alkyne‐azide cycloaddition click reaction. The synthesized iminosugars clusters were tested as multivalent inhibitors of the biologically relevant enzymes β‐glucocerebrosidase and acid α‐glucosidase, involved in Gaucher and Pompe lysosomal storage diseases, respectively. For both enzymes, all the multivalent compounds were more potent than the reference N‐hexyl deoxynojirimycin. Remarkably, final dodecavalent compound proved to be one of the best β‐glucocerebrosidase inhibitors described to date. These cyclotriphosphazene‐based deoxynojirimycin dendrimers were then evaluated as pharmacological chaperones against Gaucher disease. Not only did these multivalent constructs cross the cell membranes but they were also able to increase β‐glucocerebrosidase activity in Gaucher cells. Notably, dodecavalent compound allowed a 1.4‐fold enzyme activity enhancement at a concentration as low as 100 nM. These new monofluorocyclooctyne‐presenting dendrimers may further find numerous applications in the synthesis of multivalent objects for biological and pharmacological purposes.

show abstract

Synthesis, characterization, and computational study of novel carvacrol-based 2-aminothiol and sulfonic acid derivatives as metabolic enzyme inhibitors

Bytyqi-Damoni,

Uc,

Bora

et al. 2024

Journal of Molecular Structure

View full text Add to dashboard Cite

Fluorescence sensing and glycosidase inhibition effect of multivalent glycosidase inhibitors based on Naphthalimide-deoxynojirimycin conjugates

Cited by 4 publications

References 49 publications

Amphiphilic α-Peptoid-deoxynojirimycin Conjugate-based Multivalent Glycosidase Inhibitor for Hypoglycemic Effect and Fluorescence Imaging

Amphiphilic α-Peptoid-deoxynojirimycin Conjugate-based Multivalent Glycosidase Inhibitor for Hypoglycemic Effect and Fluorescence Imaging

Phosphorus Dendrimers for Metal‐Free Ligation: Design of Multivalent Pharmacological Chaperones against Gaucher Disease

Synthesis, characterization, and computational study of novel carvacrol-based 2-aminothiol and sulfonic acid derivatives as metabolic enzyme inhibitors

Contact Info

Product

Resources

About