- Inhibition of influenza virus infection by multivalent pentacyclic triterpene-functionalized per-O-methylated cyclodextrin conjugates
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Multivalent ligands that exhibit high binding affinity to influenza hemagglutinin (HA) trimer can block the interaction of HA with its sialic acid receptor. In this study, a series of multivalent pentacyclic triterpene-functionalized per-O-methylated cyclodextrin (CD) derivatives were designed and synthesized using 1, 3-dipolar cycloaddition click reaction. A cell-based assay showed that three compounds (25, 28 and 31) exhibited strong inhibitory activity against influenza A/WSN/33 (H1N1) virus. Compound 28 showed the most potent anti-influenza activity with IC50 of 4.7?μM. The time-of-addition assay indicated that compound 28 inhibited the entry of influenza virus into host cell. Further hemagglutination inhibition (HI) and surface plasmon resonance (SPR) assays indicated that compound 28 tightly bound to influenza HA protein with a dissociation constant (KD) of 4.0?μM. Our results demonstrated a strategy of using per-O-methylated β-CD as a scaffold for designing multivalent compounds to disrupt influenza HA protein-host receptor protein interaction and thus block influenza virus entry into host cells.
- Tian, Zhenyu,Si, Longlong,Meng, Kun,Zhou, Xiaoshu,Zhang, Yongmin,Zhou, Demin,Xiao, Sulong
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- An outer-sphere ligand for uranyl carbonate
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A novel supramolecular host for the uranyl carbonate complex has been designed and synthesized. The modified cyclodextrin host binds uranyl carbonate in water with a stability of 253 M-1.
- Prudden, Anthony R.,Lien, Nathan R.,Telford, Jason R.
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- The uncommon strong inhibition of α-glucosidase by multivalent glycoclusters based on cyclodextrin scaffolds
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The homeostasis disruption of d-glucose causes diabetes, a dramatic chronic disease worldwide. Type 1 diabetes is a successfully treatable form, where blood d-glucose is regulated by insulin treatment. In contrast type 2 diabetes, the non-insulin dependent kind, is problematic. The control of the d-glucose blood level via intestinal α-d-glucosidase inactivation can be achieved by using competitive inhibitors, such as iminosugars (e.g. acarbose) or sulfonium sugar derivatives (e.g. salacinol). Recently, an unprecedented result showed that multivalent diamond nanoparticles grafted with unmodified sugars displayed α-glucosidase inhibition at low micromolar concentrations. Herein we describe the synthesis of multivalent glycoclusters using cyclodextrins (CDs) as scaffolds and an assessment of their role as inhibitors of α-d-glucosidase. The glycoclusters were efficiently obtained from per-azido α, β and γ-CD derivatives and propargyl glycosides using click-chemistry under microwave irradiation. The methodology was successfully applied to various protected and non-protected propargylated monosaccharides, including both O- and S-glycosides, giving clear evidence of its versatility. The targeted 6-per-glycosylated CDs were isolated in moderate to excellent yields (30-90%) by silica gel chromatography. The results showed inhibition of α-glucosidase from Saccharomyces cerevisiae with IC50 values in the 32-132 μM range, lower than that of acarbose (IC50 = ～250 μM), a well-known competitive inhibitor used in the clinical treatment of type 2 diabetes. Preliminary experiments suggest a mixed-type non-competitive inhibition mode for these new glycoclusters.
- Alali, Urjwan,Vallin, Aurélie,Bil, Abed,Khanchouche, Takwa,Mathiron, David,Przybylski, Cédric,Beaulieu, Rémi,Kovensky, José,Benazza, Mohammed,Bonnet, Véronique
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- Facile preparation of a symmetric hexavalent oleanolic acid/per-O-methylated α-cyclodextrin conjugate with two conformations in solution and unambiguous NMR analysis
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A newly synthesized hexavalent oleanolic acid/per-O-methylated α-cyclodextrin conjugate shows significant differences in NMR spectra with previously synthesized analogs. Characterization of the product by 1H NMR, 13C NMR, COSY, HSQC, HMBC, TOCSY, NOE, and ROESY experiments were performed. Detailed investigations revealed that the compound has two conformations in solution and the ratio of them was 1:1. Further variable-temperature NMR study revealed that the two conformations were stable at temperature range of 273–323?K in CDCl3 solution.
- Tian, Zhenyu,Meng, Kun,Shi, Yanhong,Zhang, Naixia,Liu, Xuehui,Jin, Hongwei,Zhang, Yongmin,Zhang, Lihe,Zhou, Demin,Xiao, Sulong
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- A convenient procedure for the formation of per(6-deoxy-6-halo) cyclodextrins using the combination of tetraethylammonium halide with [Et 2NSF2]BF4
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A convenient and efficient procedure for the regioselective halogenation of the primary alcohols of cyclodextrins using the reagent combination of tetraethylammonium halide with [Et2NSF2]BF4 is described. Georg Thieme Verlag Stuttgart New York.
- Liu, Xiaofeng,Cheng, Sen,Wang, Xiaolei,Xue, Weihua
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- Novel amphiphilic cyclodextrins: Per[6-deoxy-6-(4,5-dicarboxy-1,2,3-triazol-1-yl)-2,3-di-0-methyl] derivatives
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Per[6-deoxy-6-(4,5-dicarboxy-1,2,3-triazol-1-yl)-2,3-di-0-methyl] substituted α- and β-cyclodextrins 6a and 6b were prepared by 1,3-dipolar cycloaddition reaction of the corresponding per(6-azido-6-deoxy-2,3-di-0-methyl)cyclodextrins 4a and 4b with dimethyl acetylenedicarboxylate.
- Kraus, Tomas,Budesinsky, Milos,Zavada, Jiri
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- Facial Synthesis and Bioevaluation of Well‐Defined OEGylated Betulinic Acid‐Cyclodextrin Conjugates for Inhibition of Influenza Infection
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Betulinic acid (BA) and its derivatives exhibit a variety of biological activities, especially their anti‐HIV‐1 activity, but generally have only modest inhibitory potency against influenza virus. The entry of influenza virus into host cells can be competitively inhibited by multivalent derivatives targeting hemagglutinin. In this study, a series of hexa‐, hepta‐ and octavalent BA derivatives based on α-, β-and γ-cyclodextrin scaffolds, respectively, with varying lengths of flexible oligo(ethylene glycol) linkers was designed and synthesized using a microwave‐assisted copper‐catalyzed 1,3‐di-polar cycloaddition reaction. The generated BA‐cyclodextrin conjugates were tested for their in vitro activity against influenza A/WSN/33 (H1N1) virus and cytotoxicity. Among the tested com-pounds, 58, 80 and 82 showed slight cytotoxicity to Madin‐Darby canine kidney cells with viabilities ranging from 64 to 68% at a high concentration of 100 μM. Four conjugates 51 and 69–71 showed significant inhibitory effects on influenza infection with half maximal inhibitory concentration val-ues of 5.20, 9.82, 7.48 and 7.59 μM, respectively. The structure‐activity relationships of multivalent BA‐cyclodextrin conjugates were discussed, highlighting that multivalent BA derivatives may be potential antiviral agents against influenza infection.
- Chen, Yingying,Gao, Qianqian,Liang, Shuobin,Ma, Xinyuan,Tretyakova, Elena V.,Wang, Xinchen,Xiao, Sulong,Zhang, Yongmin,Zhou, Demin
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- Method for synthesizing beta-hydroxy carbonyl compound by catalyzing asymmetric Aldol reaction in water phase
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The invention discloses a method for synthesizing a beta-hydroxy carbonyl compound by catalyzing asymmetric Aldol reaction in a water phase. The method comprises the following steps: in the water phase, catalyzing ketone and aldehyde with equal molar weig
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Paragraph 0027-0028
(2021/01/28)
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- Photo-Controllable Catalysis and Chiral Monosaccharide Recognition Induced by Cyclodextrin Derivatives
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A supramolecular catalytic system was constructed from polycationic α-cyclodextrin (6-Iz-α-CD) and gold nanoparticles (AuNP) using a supramolecular assembly strategy. The cavity of cyclodextrin is the channel by which the substrate molecules come into con
- Chen, Lei,Chen, Yong,Zhang, Yi,Liu, Yu
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supporting information
p. 7654 - 7658
(2021/03/01)
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- Synthesis of a Hexavalent Betulinic Acid Derivative as a Hemagglutinin-Targeted Influenza Virus Entry Inhibitor
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Naturally occurring pentacyclic triterpenes, such as betulinic acid (BA) and its derivatives, exhibit various pharmaceutical activities and have been the subject of great interest, in particular for their antiviral properties. Here, we found a new anti-influenza virus conjugate, hexakis 6-deoxy-6-[4-N-(3β-hydroxy-lup-20(29)-en-28-oate)aminomethyl-1H-1,2,3-triazol-1-yl]-2,3-di-O-acetyl-α-cyclodextrin (CYY1-11, 1), in a mini library of pentacyclic triterpene-cyclodextrin conjugates by performing a cell-based screening assay and then exploring the underlying mechanisms. Our results showed that conjugate 1 possessed a high-level activity against the influenza virus A/WSN/33 with an IC50 value of 5.20 μM (SI > 38.4). The study of the mechanism of action indicated that conjugate 1 inhibited viral replication by directly targeting the influenza hemagglutinin protein (KD = 1.50 μM), thus efficiently preventing the attachment of the virion to its receptors on host cells and subsequent infection. This study suggests that multivalent BA derivatives have possible use as a new class of influenza virus entry inhibitors.
- Chen, Yingying,Si, Longlong,Wang, Xinchen,Xiao, Sulong,Zhang, Bo,Zhang, Lihe,Zhang, Yongmin,Zhou, Demin,Zhu, Yinbiao
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p. 2546 - 2554
(2020/08/14)
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- MULTIVALENT FUCOSE DERIVATIVES FOR USE AS A DRUG
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The present invention relates to a compound bearing at least two fucose moieties for its use as a drug in the prevention or treatment of infections caused by Aspergillus spp, said compound having a molecular weight comprised from 0.6 to 340 kDa, in particular from 0.6 to 2 kDa or from 1 to 7 kDa or from 2 to 10 kDa or from 5 to 340 kDa.
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Page/Page column 54; 55
(2018/09/21)
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- Improved preparation of hexakis(6-deoxy)cyclomaltohexaose and heptakis(6-deoxy)cyclomaltoheptaose
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Hexakis(6-deoxy)cyclomalto-hexaose and hexakis(6-deoxy)cyclomalto-hexaose were prepared by direct halogenation of cyclodextrins, with high yields. Direct bromination of cyclomaltohexaose for 15 hours gave a 93% yield.
- Baer,Vargas Berenguel,Shu,Defaye,Gadelle,Santoyo Gonzalez
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p. 307 - 314
(2007/10/02)
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