The Synthesis of the Glycopolymers Containing Pendant D,L-Xylaric and L-Tartaric Moieties and Their Inhibition Behavior on the β-Glucuronidase Activity

Kawaguchi, Asei William; Kaida, Takafumi; Okawa, Haruki; Hashimoto, Kazuhiko

doi:10.1295/polymj.pj2008105e

Cited by 2 publications

(1 citation statement)

References 17 publications

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“…60) was dependent on the presence of carboxyl unit, type and configuration of sugar unit. Hence, glycopolymers with D-glucaric pendants linked to the polymer frame at C-1 (185), were stronger inhibitors compared to glycopolymers linked at C-5 (186) or those bearing D-gluconic (187) [253], D-mannaric (188) [254] and shorter chain D,L-xylaric (189) and L-tartaric (190) [255] pendants. However, these glycopolymers only show >60% inhibition at millimolar concentrations.…”

Section: Metal Complexes and Glycopolymersmentioning

confidence: 99%

Therapeutic significance of β-glucuronidase activity and its inhibitors: A review

Awolade

Cele

Kerru

et al. 2020

European Journal of Medicinal Chemistry

102

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BiomarkerEnzyme inhibition Molecular target Structure activity relationship a b s t r a c tThe emergence of disease and dearth of effective pharmacological agents on most therapeutic fronts, constitutes a major threat to global public health and man's existence. Consequently, this has created an exigency in the search for new drugs with improved clinical utility or means of potentiating available ones. To this end, accumulating empirical evidence supports molecular target therapy as a plausible egress and, b-glucuronidase (bGLU) e a lysosomal acid hydrolase responsible for the catalytic deconjugation of b-D-glucuronides has emerged as a viable molecular target for several therapeutic applications. The enzyme's activity level in body fluids is also deemed a potential biomarker for the diagnosis of some pathological conditions. Moreover, due to its role in colon carcinogenesis and certain drug-induced dose-limiting toxicities, the development of potent inhibitors of bGLU in human intestinal microbiota has aroused increased attention over the years. Nevertheless, although our literature survey revealed both natural products and synthetic scaffolds as potential inhibitors of the enzyme, only few of these have found clinical utility, albeit with moderate to poor pharmacokinetic profile. Hence, in this review we present a compendium of exploits in the present millennium directed towards the inhibition of bGLU. The aim is to proffer a platform on which new scaffolds can be modelled for improved bGLU inhibitory potency and the development of new therapeutic agents in consequential.

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Section: Metal Complexes and Glycopolymersmentioning

confidence: 99%

Therapeutic significance of β-glucuronidase activity and its inhibitors: A review

Awolade

Cele

Kerru

et al. 2020

European Journal of Medicinal Chemistry

102

View full text Add to dashboard Cite

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Glycomonomeric and Glycopolymeric Inhibitors for β-Glucuronidase. π–π Stacking Interaction, Polymeric Effect, and Plausible Conformation

Kawaguchi¹,

Okawa²,

Hashimoto³

2011

Bulletin of the Chemical Society of Japan

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N-p-Vinylbenzyl-6-d-glucaramic acid (VB-6-d-GlcaH, 1) and its corresponding polymer, P(VB-6-d-GlcaH-co-AAm) (2), were found to inhibit β-glucuronidase activity more efficiently than d-glucaro-6,3-lactone, while the inhibition ability of N-butyl-6-d-glucaramic acid (Butyl-6-d-GlcaH, 3) on the enzyme activity was seriously lower than that of the lactone. The π–π stacking interaction between the styryl part of 1 and Trp587 of β-glucuronidase was confirmed by the blue shift detected on fluorescence spectrophotometry and the observation of the 3D motif for the active site with the glycomonomer, which must enhance the inhibition ability of the enzyme. In the case of 2, however, such a shift was not observed, which indicated that the effective inhibition of 2 was induced not by the π–π stacking interaction but a polymeric effect. Based on these results and our previous work, plausible conformations of 1 and 2 fitting in β-glucuronidase were proposed.

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The Synthesis of the Glycopolymers Containing Pendant D,L-Xylaric and L-Tartaric Moieties and Their Inhibition Behavior on the β-Glucuronidase Activity

Cited by 2 publications

References 17 publications

Therapeutic significance of β-glucuronidase activity and its inhibitors: A review

Therapeutic significance of β-glucuronidase activity and its inhibitors: A review

Glycomonomeric and Glycopolymeric Inhibitors for β-Glucuronidase. π–π Stacking Interaction, Polymeric Effect, and Plausible Conformation

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