Selective Golgi α-mannosidase II inhibitors: N-alkyl substituted pyrrolidines with a basic functional group

New Journal of Chemistry, Год журнала: 2021, Номер 45(24), С. 10940 - 10951

Опубликована: Янв. 1, 2021

Enzymatic assays, molecular modeling and NMR studies of novel 1,4-dideoxy-1,4-imino-l-lyxitols provided new information on the GH38 family enzyme inhibitors their selectivity.

Язык: Английский

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Multivalent Pyrrolidine Iminosugars: Synthesis and Biological Relevance

Molecules, Год журнала: 2022, Номер 27(17), С. 5420 - 5420

Опубликована: Авг. 24, 2022

Recently, the strategy of multivalency has been widely employed to design glycosidase inhibitors, as glycomimetic clusters often induce marked enzyme inhibition relative monovalent analogs. Polyhydroxylated pyrrolidines, one most studied classes iminosugars, are an attractive moiety due their potent and specific glycosidases glycosyltransferases, which associated with many crucial biological processes. The development multivalent pyrrolidine derivatives inhibitors resulted in several promising compounds that stand out. Herein, we comprehensively summarized different synthetic approaches preparation clusters, from total synthesis divalent iminosugars complex architectures bearing twelve motifs. Enzyme inhibitory properties effects these synthesized were further discussed, especially for some less therapeutically relevant enzymes. We envision this comprehensive review will help extend applications future studies.

Язык: Английский

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Carbohydrate‐Based Therapeutics for Lysosomal Storage Disorders

Опубликована: Сен. 5, 2023

Lysosomal Storage Diseases (LSDs) are a group of metabolic disorders caused by loss-of-function mutations in lysosomal enzyme-encoding genes, which leads to accumulation unmetabolized substrates the lysosomes, cell disfunction and consequent severe symptoms. The currently most employed treatments for LSDs, namely Enzyme Replacement Therapy (ERT), Substrate Reduction innovative Pharmacological Chaperone (PCT), all employ carbohydrate-based compounds their preparation or as active ingredient. This chapter collects relevant vitro , pre-clinical, clinical studies conducted essentially on iminosugars (sugar mimics with nitrogen atom replacing endocyclic oxygen), aim developing therapeutics LSDs. countless options design preparations PCs, together early stage understanding mechanism action, makes investigation PCs treatment LSDs main topic chapter. account is organized accordingly classification into Mucopolysaccharidoses, Sphingolipidoses, Glycogen Disorders, Glycoproteinoses. For each disorder, structure biological activity reported commented.

Язык: Английский

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Stereocontrolled synthesis of new iminosugar lipophilic derivatives and evaluation of biological activities

Carbohydrate Research, Год журнала: 2023, Номер 534, С. 108984 - 108984

Опубликована: Ноя. 15, 2023

Iminosugars' similarity to carbohydrates determines the exceptional potential for this class of polyhydroxylated alkaloids serve as drug candidates a wide variety diseases such diabetes, lysosomal storage diseases, cancer, bacterial and viral infections. The presence lipophilic substituents has significant impact on their biological activities. This work reports synthesis three new pyrrolidine derivatives O-alkylated in C-6 position. activities our iminosugars' collection were tested two cancer cell lines and, due pharmaceutical potential, model yeast system Saccharomyces cerevisiae assess toxicity.

Язык: Английский

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New α-galactosidase-inhibiting aminohydroxycyclopentanes

RSC Advances, Год журнала: 2021, Номер 11(26), С. 15943 - 15951

Опубликована: Янв. 1, 2021

A concise and robust synthesis of new cyclopentanoid competitive inhibitors α-galactosidases related to Fabry's disease other α-galactosidase disorders.

Язык: Английский

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Multivalent resorcinarene clusters decorated with DAB-1 inhitopes: targeting Golgi α-mannosidase fromDrosophila melanogaster

Organic Chemistry Frontiers, Год журнала: 2021, Номер 8(23), С. 6648 - 6656

Опубликована: Янв. 1, 2021

Resorcinarene@DAB-1 clusters show a remarkable multivalent effect towards GMIIb over other α-mannosidases, due to rebinding mechanism: two DAB-1 units of the cluster bind Zn-sites dimeric protein in an alternate way.

Язык: Английский

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Carbohydrates mimetics: enzyme inhibitors and target molecules in several diseases

Elsevier eBooks, Год журнала: 2021, Номер unknown, С. 547 - 577

Опубликована: Ноя. 26, 2021

Язык: Английский

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