Synthesis of kifunensine thioanalogs and their inhibitory activities against HIV-RT and α-mannosidase

Chen, Hua; Li, Rui; Liu, Zhenying; Wei, Sinan; Zhang, Hongzhi; Li, Xiaoliu

doi:10.1016/j.carres.2012.10.017

Cited by 15 publications

(2 citation statements)

References 44 publications

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“…Marchiori and co-workers have synthesized a series of triazole-linked galactosyl arylsulfonamides 16-22 by the click cycloaddition reaction of the azide-arylsulfonamides 1-7 with the alkyne-based sugar 3-O-propynyl-βGalOMe 8 17 followed by deacetylation of compounds 9-15 (Scheme 1). 18 Scheme 1 Synthesis of triazole-linked galactosyl arylsulfonamides [16][17][18][19][20][21][22] The Trypanosoma cruzi cell invasion inhibition experiments revealed that, the compounds 18 and 20 with the corresponding 5-methylisoxazole and 2,4-dimethoxypyrimidine groups displayed lower values of infection index (~20) in T. cruzi cell invasion inhibition assays among the synthesized compounds 16-22, these compounds also displayed higher binding affinities to galectin-3 (EC50 17-18 µM) in Corning Epic labelfree assays. So, the discovery of compounds 3 and 5 as possible galectin-3 binding-related T. cruzi cell invasion blockers reveal galectin-3 as a crucial host target for the development of new antitrypanosomal medicines.…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in the Synthesis of Bioactive Glycohybrids via Click-Chemistry

Singh

Tyagi

Mishra

et al. 2023

SynOpen

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Carbohydrates, traditionally known for their energy-providing role, have gained significant attention in drug discovery due to their diverse bioactivities and stereodiversity. However, pure carbohydrate molecules often exhibit limited bioactivity and suboptimal chemical and physical characteristics. To address these challenges, functional groups with bioactive scaffolds have been incorporated into carbohydrate to enhance their bioactivity and improve their overall properties. Among the various synthetic methods available, click chemistry has emerged as a powerful tool for the synthesis of carbohydrate-containing bioactive scaffolds, known as glycohybrids. Click chemistry offers several advantages, including high chemo- and regioselectivity, mild reaction conditions, easy purification and compatibility with multiple functional groups. In the present review, we have emphasized the recent advances and most pertinent research on the development of 1,2,3-triazole-containing glycohybrids using click reaction, their biological evaluations and the structure-activity relationship during 2017-2023. These newly synthesised glycohybrids could potentially be developed as new chemical entities (NCE) in pharmaceutical chemistry and may encourage the use of carbohydrates in drug discovery processes. 1 Introduction 2 CuAAC click chemistry mediated synthesis of triazole based glycohybrids and their biological activities 3 Conclusions and perspective

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Section: Introductionmentioning

confidence: 99%

Recent Advances in the Synthesis of Bioactive Glycohybrids via Click-Chemistry

Singh

Tyagi

Mishra

et al. 2023

SynOpen

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“…67 The sp 2 -hybridized character is also observed in some natural products such as kifunensine, a potent inhibitor of class I α-mannosidase. 69,70 To check this strategy for the particular case of hexosaminidases, we synthesized a series of ureido-DNJNAc derivatives (10). In addition to a much lower basic character at the endocyclic nitrogen, conversion of an amine into a urea offers flexibility in the choice of substituents, which can be taken advantage of to optimize the inhibitory capacity and the pharmacokinetic behavior.…”

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confidence: 99%

Stereoselective synthesis of 2-acetamido-1,2-dideoxynojirimycin (DNJNAc) and ureido-DNJNAc derivatives as new hexosaminidase inhibitors

et al. 2015

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2-Acetamido-1,2-dideoxyiminosugars are selective and potent inhibitors of hexosaminidases and therefore show high therapeutic potential for the treatment of various diseases, including several lysosomal storage disorders. A stereoselective synthesis of 2-acetamido-1,2-dideoxynojirimycin (DNJNAc), the iminosugar analog of N-acetylglucosamine, with high overall yield is here described. This novel procedure further allowed accessing ureidoDNJNAc conjugates through derivatization of the endocyclic amine on a key pivotal intermediate. Remarkably, some of the ureido-DNJNAc representatives behaved as potent and selective inhibitors of β-hexosaminidases, including the human enzyme, being the first examples of neutral sp 2 -iminosugar-type inhibitors reported for these enzymes. Moreover, the amphiphilic character of the new ureido-DNJNAc is expected to confer better drug-like properties.

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Functionalized High Mannose‐Specific Lectins for the Discovery of Type I Mannosidase Inhibitors

et al. 2021

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An engineered cyanovirin‐N homologue that exhibits specificity for high mannose N‐glycans has been constructed to aid type I α 1,2‐mannosidase inhibitor discovery and development. Engineering the lectins C‐terminus permitted facile functionalization with fluorophores via a sortase and click strategy. The resulting lectin constructs exhibit specificity for cells presenting high mannose N‐glycans. Importantly, these lectin constructs can also be applied to specifically assess changes in cell surface glycosylation induced by type I mannosidase inhibitors. Testing the utility of these lectin constructs led to the discovery of type I mannosidase inhibitors with nanomolar potency. Cumulatively, these findings reveal the specificity and utility of the functionalized cyanovirin‐N homologue constructs, and highlight their potential in analytical contexts that require high mannose‐specific lectins.

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Synthesis of kifunensine thioanalogs and their inhibitory activities against HIV-RT and α-mannosidase

Cited by 15 publications

References 44 publications

Recent Advances in the Synthesis of Bioactive Glycohybrids via Click-Chemistry

Recent Advances in the Synthesis of Bioactive Glycohybrids via Click-Chemistry

Stereoselective synthesis of 2-acetamido-1,2-dideoxynojirimycin (DNJNAc) and ureido-DNJNAc derivatives as new hexosaminidase inhibitors

Functionalized High Mannose‐Specific Lectins for the Discovery of Type I Mannosidase Inhibitors

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