Sialyl Lewisx analogs based on a quinic acid scaffold as the fucose mimic

Girard, Christian; Dourlat, Jennifer; Savarin, Aline; Surcin, Christine; Leue, Stefanie; Escriou, Virginie; Largeau, Céline; Herscovici, Jean; Scherman, Daniel

doi:10.1016/j.bmcl.2005.05.004

Cited by 20 publications

(21 citation statements)

References 17 publications

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“…67,68 These same authors showed that the presence of a carboxylic acid functional group was necessary for interaction with the selectins. 67,68 A seriels of QA amides will be prepared, then go to biological screening against our NF-κB activity HTS System. QA amide leads will form a new template for anti-inflammatory agents.…”

Section: Synthesis Of Qa Amide Analogsmentioning

confidence: 99%

“…See Figure 1-3 from Vink et al 66 Recent work has demonstrated an interaction of QA derivatives with the carbohydrate binding proteins (lectins) involved in key leukocyte-endothelial cell interactions. 67,68 Tetrasaccharide sialyl Lewis x (sLex) ligands found on leukocytes contain sialic acid, L-fucose, and galactose which are essential for calcium-mediated binding of sLex to the carbohydrate binding proteins E, P, and L-selectin. Tetrasaccharide sLex exhibits a poor pharmacokinetic profile and thus cannot be developed as a selectin inhibitor.…”

Section: Biological Activities Of Qa and Its Derivativesmentioning

confidence: 99%

“…A search for druggable sLex mimetics led to the substitution of QA for fucose since the hydroxyl groups of QA mimic hydroxyl groups of fucose which make key interactions with protein side chains that bind calcium. 67,68 Selective QA analogs were shown to decrease leukocyte rolling in response to LPS in an intravital microscopy mouse model and to decrease neutrophil influx in a murine thioglycollate-induced peritonitis model. 68 Others have shown that selective QA analogs interact weakly with both P-and E-selectin using HL-60 cells.…”

Section: Biological Activities Of Qa and Its Derivativesmentioning

confidence: 99%

“…A review prepared by Barco has comprehensively covered QA chemistry literature up to the beginning of 1997. synthesized QA derivatives as sialyl lewis x -mimicking selectin inhibitors in order to target E-selectin. 67,68 Kim made analogues as influenza neuraminidase inhibitors with potent anti-anfluenza activity. 91 Sanchez-Sixto and Metaferia made compounds to kill Mycobacterium tuberculosis.…”

Section: Synthesis Of Qa and Its Derivativesmentioning

confidence: 99%

“…67,68,114 The synthesis of the lactone 2 was carried out using PTSA in refluxing benzene and DMF according to the procedure of Neelu Kaila et al with minor revision. The lactone was then allowed to react with N-propyl amine with acetic acid at 85C and the resulting amide 3 was purified using flash chromatography.…”

Section: Synthesis Of Quinic Acid Amidesmentioning

confidence: 99%

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Discovery of Quinic Acid Derivatives as Oral Anti-inflammatory Agents

Zeng¹

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Section: Synthesis Of Qa Amide Analogsmentioning

confidence: 99%

Section: Biological Activities Of Qa and Its Derivativesmentioning

confidence: 99%

Section: Biological Activities Of Qa and Its Derivativesmentioning

confidence: 99%

Section: Synthesis Of Qa and Its Derivativesmentioning

confidence: 99%

Section: Synthesis Of Quinic Acid Amidesmentioning

confidence: 99%

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Discovery of Quinic Acid Derivatives as Oral Anti-inflammatory Agents

Zeng¹

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Carbohydrate‐based Biomedical Copolymers for Targeted Delivery of Anticancer Drugs

David

2010

Israel Journal of Chemistry

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A variety of strategies and carrier molecules have been used to direct therapeutic agents to tumor sites. The incorporation of a specific targeting moiety to drug carrier may result in active drug uptake by malignant cells. Carbohydrates are important mediators of cell–cell recognition events and have been implicated in related processes such as cell signaling regulation, cellular differentiation, and immune response. The biocompatibility of carbohydrates and their ability to be specifically recognized by cell‐surface receptors indicate their potential utility as ligands in targeted drug delivery for therapeutic applications. Yet, carbohydrates are not ideal targeting ligands because they are difficult to synthesize, bind weakly to carbohydrate receptors, and are prone to suffer from enzyme degradation due to labile glycosidic linkages. This review describes the design and development of HPMA‐based biomedical copolymers to facilitate the selective delivery of drugs to tumor tissues via carbohydrate–endogenous lectin interactions. Various carbohydrate‐decorated HPMA copolymer–drug conjugates are presented and the application of the copolymers for drug delivery is discussed. Current efforts to increase the affinity of carbohydrate ligands for their target receptors through multivalent display are also discussed. These novel HPMA copolymer carbohydrate conjugates hold promise as clinically relevant drug delivery systems for cancer therapy.

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Quinic Acid‐Conjugated Nanoparticles Enhance Drug Delivery to Solid Tumors via Interactions with Endothelial Selectins

Lee

Seo

et al. 2018

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Current nanoparticle (NP) drug carriers mostly depend on the the enhanced permeability and retention (EPR) effect for selective drug delivery to solid tumors. However, in the absence of persistent EPR effect, the peritumoral endothelium can function as an access barrier to tumors and negatively affect the effectiveness of NPs. In recognition of the peritumoral endothelium as a potential barrier in drug delivery to tumors, poly(lactic-co-glycolic acid) NPs are modified with a quinic acid (QA) derivative, synthetic mimic of selectin ligands. QA-decorated NPs (QA-NP) interact with human umbilical vein endothelial cells (HUVECs) expressing E-/P-selectins and induce transient increase in endothelial permeability to translocate across the layer. QA-NP reach selectin-upregulated tumors, achieving greater tumor accumulation and paclitaxel (PTX) delivery than polyethylene glycol-decorated NPs (PEG-NP). PTX-loaded QA-NP show greater anti-cancer efficacy than Taxol® or PTX-loaded PEG-NP at the equivalent PTX dose in different animal models and dosing regimens. Repeated dosing of PTX-loaded QA-NP for two weeks result in complete tumor remission in 40-60% of MDA-MB-231 tumor-bearing mice, while those receiving control treatments succumb to death. QA-NP can exploit the interaction with selectin-expressing peritumoral endothelium and deliver anti-cancer drugs to tumors to a greater extent than the level currently possible with the EPR effect.

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Sialyl Lewisx analogs based on a quinic acid scaffold as the fucose mimic

Cited by 20 publications

References 17 publications

Discovery of Quinic Acid Derivatives as Oral Anti-inflammatory Agents

Discovery of Quinic Acid Derivatives as Oral Anti-inflammatory Agents

Carbohydrate‐based Biomedical Copolymers for Targeted Delivery of Anticancer Drugs

Quinic Acid‐Conjugated Nanoparticles Enhance Drug Delivery to Solid Tumors via Interactions with Endothelial Selectins

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