29390-67-8Relevant articles and documents
Preparation, characterization and biological evaluation of β-cyclodextrin-biotin conjugate based podophyllotoxin complex
Zhao, Xiu,Qiu, Neng,Ma, Yingyu,Liu, Junda,An, Lianying,Zhang, Teng,Li, Ziqin,Han, Xu,Chen, Lijuan
, (2021)
Podophyllotoxin is a natural occurring aryltetralin lignin with pronounced cytotoxic activity. However, its clinical application for cancer treatment has been blocked due to its poor water solubility and selectivity. In this work, biotin as a tumor specific ligand was coupled with β-cyclodextrin and the resulting biotin modified β-cyclodextrin was used to complex with podophyllotoxin to improve its aqueous solubility and tumor selectivity. The solubility of β-cyclodextrin was greatly enhanced(>16 times) by conjugating with biotin. podophyllotoxin/ mono-6-biotin-amino-6-deoxy-β-cyclodextrin inclusion complex was prepared by freeze-drying method and the complex behavior between mono-6-biotin-amino-6-deoxy-β-cyclodextrin and podophyllotoxin was studied by water solubility, phase solubility, Job's plot, UV spectroscopy, Proton Nuclear Magnetic Resonance, Rotating-frame Overhauser Effect Spectroscopy, Powder X-ray diffraction and Scanning electron microscopy. The solubility of podophyllotoxin/ mono-6-biotin-amino-6-deoxy-β-cyclodextrin complex was greatly improved(9 times) compared with Podophyllotoxin. The stability constant of podophyllotoxin/ mono-6-biotin-amino-6-deoxy-β-cyclodextrin complex (Ks= 415.29 M?1) was 3.2 times that of podophyllotoxin/β-cyclodextrin complex. The possible inclusion mode of podophyllotoxin/mono-6-biotin-amino-6-deoxy-β-cyclodextrin complex was inferred from the Proton Nuclear Magnetic Resonance and Rotating-frame Overhauser Effect Spectroscopy. The cellular uptake study showed that the introduction of biotin increased the cellular uptake of rhodamine-B/mono-6-biotin-amino-6-deoxy-β-cyclodextrin complex. Moreover, cell cytotoxicity study showed that the antitumor activity of podophyllotoxin/ mono-6-biotin-amino-6-deoxy-β-cyclodextrin complex was more potent than podophyllotoxin/β-cyclodextrin complex and free podophyllotoxin. The superior water solubility and enhanced cytotoxicity suggested that the mono-6-biotin-amino-6-deoxy-β-cyclodextrin associated inclusion complex might be a potential and promising delivery system for hydrophobic chemotherapeutics such as podophyllotoxin.
Aminated β-cyclodextrin-grafted Fe3O4-loaded gambogic acid magnetic nanoparticles: Preparation, characterization, and biological evaluation
Fang, Wei,Dai, Ya Ji,Wang, Ting,Gao, Hai Tao,Huang, Peng,Yu, Juan,Huang, He Ping,Wang, Dian Lei,Zong, Wei Lu
, p. 27136 - 27146 (2019)
Based on aminated β-cyclodextrin (6-NH2-β-CD)-grafted Fe3O4 and gambogic acid (GA) clathrate complexes, a nanoparticle delivery system was developed with the aim to achieve low irritation, strong targeting, and high bioavailability of a gambogic acid magnetic nanopreparation. 6-NH2-β-CD grafted onto Fe3O4 MNPs was demonstrated by high-resolution transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, zeta potential, and magnetic measurements. The average particle size of the Fe3O4?NH2-β-CD MNPs was 147.4 ± 0.28 nm and the PDI was 0.072 ± 0.013. The encapsulation efficiency, drug loading, zeta potential, and magnetic saturation values of the Fe3O4?NH2-β-CD MNPs were 85.71 ± 3.47%, 4.63 ± 0.04%, -29.3 ± 0.42 mV, and 46.68 emu g-1, respectively. Compared with free GA, the in vitro release profile of GA from Fe3O4?NH2-β-CD MNPs was characterized by two phases: an initial fast release and a delayed-release phase. The Fe3O4?NH2-β-CD MNPs displayed continuously increased cytotoxicity against HL-60 and HepG2 cell lines in 24 h, whereas the carrier Fe3O4?NH2-β-CD MNPs showed almost no cytotoxicity, indicating that the release of GA from the nanoparticles had a sustained profile and Fe3O4?NH2-β-CD MNPs as a tumor tissue-targeted drug delivery system have great potential. Besides, blood vessel irritation tests suggested that the vascular irritation could be reduced by the use of Fe3O4?NH2-β-CD MNPs encapsulation for GA. The t1/2 and the AUC of the Fe3O4?NH2-β-CD?GA MNPs were found to be higher than those for the GA solution by approximately 2.71-fold and 2.42-fold in a pharmacokinetic study, respectively. The better biocompatibility and the combined properties of specific targeting and complexation ability with hydrophobic drugs make the Fe3O4?NH2-β-CD MNPs an exciting prospect for the targeted delivery of GA.
pH-sensitive β-cyclodextrin derivatives for the controlled release of Podophyllotoxin
Gao, Chuanzhu,Li, Fanjie,Liao, Xiali,Yang, Bo,Yang, Jing,Yang, Lei,Yang, Waixiang,Zhao, Yulin
, (2021)
An effective tumor targeting drug delivery systems was designed and synthesized by conjugating pH-sensitive maleamide derivatives to Mono-(6-deoxy-6-amino)-β-CD. Their characteristics and inclusion behaviors with insoluble anticancer drug PPT were investigated in both solution and solid state by means of 1H NMR and 2D-ROESY, XRD, DSC and SEM, which reveal PPT is successfully encapsulated in the cavity of CD derivatives with different stability constants (Ks). Water solubility of PPT are significantly increased to 60.35 and 22.89 mg·mL?1 after formation of inclusion complexes with host-1 and host-2, compared with free PPT (0.12 mg·mL?1). Their acid-controlled release has been studied in vitro by 1H NMR and UV-Vis spectra, living cells incubated with host 1-2 were observed by Inverted fluorescence microscope to confirm pH-response releasing. Moreover, host-1/PPT and host-2/PPT maintain effective cell proliferation inhibition to human cancer, while their cytotoxicity to normal cell is significantly reduced. Our work shows inspiring potential in tumor-targeted delivery and acid-controlled release of PPT both in vitro.
Fluorescent sensors of molecular recognition. Modified cyclodextrins capable of exhibiting guest-responsive twisted intramolecular charge transfer fluorescence
Hamasaki, Keita,Ikeda, Hiroshi,Nakamura, Asao,Ueno, Akihiko,Toda, Fujio,Suzuki, Iwao,Osa, Tetsuo
, p. 5035 - 5040 (1993)
α-, β-, and γ-cyclodextrin derivatives bearing a p-(dimethylamino)benzoyl (DMAB) moiety (DMAB-αCyD, DMAB-βCyD, and DMAB-γCyD, respectively) have been synthesized as fluorescent sensors of molecular recognition. These compounds show dual fluorescence emission arising from normal planar (NP) and twisted intramolecular charge transfer (TICT) exited states, and among them strong TICT emission was observed for DMAB-βCyD. The induced circular dichroism spectra of the derivatives suggest that only DMAB-βCyD among other derivatives binds the DMAB moiety into its own cavity, forming an intramolecular inclusion complex. This conformation was confirmed by the analysis of its 1H-NMR data and was related to its strong TICT emission. The intensity of the TICT emission of DMAB-βCyD decreased markedly with increasing the concentration of cyclic alchols, monoterpenes, or steroids. This observation was explained by the guest-induced location change of the DMAB moiety from inside to outside of the cavity. Since the TICT emission intensity depended on the size, shape, and polarity of the guest molecules, DMAB-βCyD was useful as a fluorescent chemosensor of molecular recognition.
Insight into the Excitation-Dependent Fluorescence of Carbon Dots
Divya, Sasi,Narayan, Satya,Ainavarapu, Sri Rama Koti,Khushalani, Deepa
, p. 984 - 990 (2019)
High quantum yield, photoluminescence tunability, and sensitivity to the environment are a few distinct trademarks that make carbon nanodots (CDs) interesting for fundamental research, with potential to replace the prevalent inorganic semiconductor quantum dots. Currently, application and fundamental understanding of CDs are constrained because it is difficult to make a quantitative comparison among different types of CDs simply because their photoluminescence properties are directly linked to their size distribution, the surface functionalization, the carbon core structures (graphitic or amorphous) and the number of defects. Herein, we report a facile one-step synthesis of mono-dispersed and highly fluorescent nanometre size CDs from a ‘family’ of glucose-based sugars. These CDs are stable in aqueous solutions with photoluminescence in the visible range. Our results show several common features in the family of CDs synthesized in that the fluorescence, in the visible region, is due to a weak absorption in the 300–400 nm from a heterogeneous population of fluorophores. Fluorescence quenching experiments suggest the existence of not only surface-exposed fluorophores but more importantly solvent inaccessible fluorophores present within the core of CDs. Interestingly, time-resolved fluorescence anisotropy experiments directly suggest that a fast exchange of excitation energy occurs that results in a homo-FRET based depolarization within 150 ps of excitation.
Supramolecular self-assembled aggregates formed by pentacosa-10,12-diynyl amidomethyl-β-cyclodextrin
Cho, Eunae,Kim, Hwanhee,Yang, Jee Eun,Jun, Bong-Hyun,Paik, Seung R.,Jung, Seunho
, p. 37 - 42 (2014)
Mono[6-deoxy-6-(pentacosa-10,12-diynyl amidomethyl)]-β-cyclodextrin was successfully synthesized by reacting mono-6-amino-6-deoxy-β- cyclodextrin with N-hydroxysuccinimide ester of 10,12-pentacosadiynoic acid in DMF. The modified β-cyclodextrin self-assembled and aggregated to form a worm-like supramolecular structure, and the novel supramolecular aggregates were studied using 2D nuclear magnetic resonance spectroscopy, X-ray powder diffraction, thermogravimetry, and electron microscopy. Interestingly, the synthesized pentacosa-10,12-diynyl amidomethyl-β-cyclodextrin formed columnar type self-aggregates and it was clearly differentiated from cage-like structure of native β-cyclodextrin.
Synthesis of lipophosphoramidyl-cyclodextrins and their supramolecular properties
Gervaise, Cédric,Bonnet, Véronique,Wattraint, Olivier,Aubry, Fréderic,Sarazin, Catherine,Jaffrès, Paul-Alain,Djeda?ni-Pilard, Florence
, p. 66 - 74 (2012)
The synthesis of lipophosphoramidyl-β-CD was obtained by an Atherton-Todd (AT) reaction that involved dioleylphosphite and either functionalized permethylated or native β-cyclodextrin. This AT reaction that produced dioleylphosphoramide by making use of the amino group grafted on cyclodextrin, was optimized for these cyclic oligosaccharides. These new amphiphilic compounds were fully characterized, and their self-assembling properties were investigated: the mean size diameter and polydispersity measured by Dynamic Light Scattering (DLS) were affected by the nature of the aqueous media and the temperature of storage. The encapsulation properties of these nanoparticles have been evaluated using carboxyfluorescein and scopolamine derivatives as model of guests.
Synthesis and immunostimulatory activity of sugar-conjugated TLR7 ligands
Baba, Akihito,Wakao, Masahiro,Shinchi, Hiroyuki,Chan, Michael,Hayashi, Tomoko,Yao, Shiyin,Cottam, Howard B.,Carson, Dennis A.,Suda, Yasuo
, (2020)
Toll-like receptors (TLRs) are a type of pattern recognition receptors (PRRs), which are activated by recognizing pathogen-associated molecular patterns (PAMPs). The activation of TLRs initiates innate immune responses and subsequently leads to adaptive immune responses. TLR agonists are effective immuomodulators in vaccine adjuvants for infectious diseases and cancer immunotherapy. In exploring hydrophilic small molecules of TLR7 ligands using the cell-targeted property of a vaccine adjuvant, we conjugated 1V209, a small TLR7 ligand molecule, with various low or middle molecular weight sugar molecules that work as carriers. The sugar-conjugated 1V209 derivatives showed increased water solubility and higher immunostimulatory activity in both mouse and human cells compared to unmodified 1V209. The improved immunostimulatory potency of sugar-conjugates was attenuated by an inhibitor of endocytic process, cytochalasin D, suggesting that conjugation of sugar moieties may enhance the uptake of TLR7 ligand into the endosomal compartment. Collectively our results support that sugar-conjugated TLR7 ligands are applicable to novel drugs for cancer and vaccine therapy.
Synthesis, characterization and biological activity of Rhein-cyclodextrin conjugate
Liu, Manshuo,Lv, Pin,Liao, Rongqiang,Zhao, Yulin,Yang, Bo
, p. 239 - 244 (2017)
Cyclodextrin conjugate complexation is a useful method to enhance the solubility and absorption of poorly soluble drugs. A series of new Rhein-β-cyclodextrin conjugates (Rh-CD conjugates) have been synthesized and examined. Rhein is covalently linked with the β-CD by amido linkage in a 1:1 molar ratio. The conjugates were characterized by 1H NMR, 13C NMR, HRMS, powder X-ray diffraction (powder XRD) as well as thermogravimetric analysis (TGA). The results reveal that incorporation of β-CD could improve the aqueous solubility of Rhein and the cytotoxicity against hepatocellular carcinoma (HepG2) cell line as well as antibacterial activity against three organisms. The improved biological activity and the satisfactory water solubility of the conjugates will be potentially useful for developing novel drug-cyclodextrin conjugates, such as herbal medicine.
Synthesis and inclusion properties study of some mono 6-amino β-cyclodextrin dimers bridged by N,N-succinyldiamide linkers
Hocquelet, Celine,Jankowski, Christopher K.,Pelletier, Andre Lucien,Tabet, Jean-Claude,Lamouroux, Christine,Berthault, Patrick
, p. 75 - 84 (2011)
Methylated and partially methylated cyclodextrin homo- and heterodimers linked by diamidosuccinic bridges were synthesised and their inclusion properties were evaluated using NMR and isothermic microcalorimetric measurements ITC. The selective binding of ligands, such as bisadamantyl derivatives, to the cavities of unprotected cyclodextrin dimers showed the equimolar formation of bidendate inclusion complexes (2:2, two ligand guest to two cavities host).
Self-assembly PEGylation retaining activity (SPRA) technology via a host-guest interaction surpassing conventional PEGylation methods of proteins
Hirotsu, Tatsunori,Higashi, Taishi,Hashim, Irhan Ibrahim Abu,Misumi, Shogo,Wada, Koki,Motoyama, Keiichi,Arima, Hidetoshi
, p. 368 - 376 (2017)
Polyethylene glycol (PEG) modification (PEGylation) is one of the best approaches to improve the stabilities and blood half-lives of protein drugs; however, PEGylation dramatically reduces the bioactivities of protein drugs. Here, we present "self-assembly PEGylation retaining activity" (SPRA) technology via a host-guest interaction between PEGylated β-cyclodextrin (PEG-β-CyD) and adamantane-appended (Ad) proteins. PEG-β-CyD formed stable complexes with Ad-insulin and Ad-lysozyme to yield SPRAinsulin and SPRA-lysozyme, respectively. Both SPRA-proteins showed high stability against heat and trypsin digest, comparable with that of covalently PEGylated protein equivalents. Importantly, the SPRA-lysozyme possessed ca. 100% lytic activity, whereas the activity of the covalently PEGylated lysozyme was ca. 23%. Additionally, SPRA-insulin provided a prolonged and peakless blood glucose profile when compared with insulin glargine. It also showed no loss of activity. In contrast, the covalently PEGylated insulin showed a negligible hypoglycemic effect. These findings indicate that SPRA technology has potential as a generic method, surpassing conventional PEGylation methods for proteins.
Effects of temperature and host concentration on the supramolecular enantiodifferentiating [4 + 4] photodimerization of 2-anthracenecarboxylate through triplet-triplet annihilation catalyzed by Pt-modified cyclodextrins
Rao, Ming,Wu, Wanhua,Yang, Cheng
, (2019)
Visible-light-driven photocatalytic supramolecular enantiodifferentiating dimerization of 2-anthracenecarboxylic acid (AC) through triplet-triplet annihilation (TTA), mediated by the Schiff base Pt(II) complex (Pt-1, Pt-2, and Pt-3) was studied. The host concentration and the temperature effects on the stereoselectivity were comprehensively investigated. Increasing the concentration of sensitizers/hosts significantly enhanced the conversion of the photoreaction but led to reduced enantioselectivities of the chiral photodimers 2 and 3 when the photoreaction was triggered by a 532 nm laser, which was in contrast with the results obtained by direct irradiation of AC with a 365 nm light-emitting diode (LED) lamp, due to the aggregation of the sensitizer/host in water. The cyclization of AC through triplet-triplet annihilation displayed significant temperature dependency when Pt-3 was employed as the sensitizer/host. Increasing the temperature from 0 ?C to 30 ?C with 5% equiv. of Pt-3 led to a great increase of the ee of 2 from 2.1% to 31.6%. However, hardly any temperature dependency was observed when the photodimerization was mediated by other sensitizers and/or hosts, or the photoreaction was triggered directly with a 365 nm LED lamp.
A cyclodextrin-capped histone deacetylase inhibitor
Amin, Jahangir,Puglisi, Antonino,Clarke, James,Milton, John,Wang, Minghua,Paranal, Ronald M.,Bradner, James E.,Spencer, John
, p. 3346 - 3348 (2013)
We have synthesized a β-cyclodextrin (βCD)-capped histone deacetylase (HDAC) inhibitor 3 containing an alkyl linker and a zinc-binding hydroxamic acid motif. Biological evaluation (HDAC inhibition studies) of 3 enabled us to establish the effect of replacing an aryl cap (in SAHA (vorinostat,)) 1 by a large saccharidic scaffold "cap". HDAC inhibition was observed for 3, to a lesser extent than SAHA, and rationalized by molecular docking into the active site of HDAC8. However, compound 3 displayed no cellular activity.
β-Biguanidinium-cyclodextrin: A supramolecular mimic of mitochondrial ADP/ATP carrier protein
Chen, Huo-Yan,Zhao, Meng,Tan, Jia-Heng,Huang, Zhi-Shu,Liu, Gao-Feng,Ji, Liang-Nian,Mao, Zong-Wan
, p. 2378 - 2382 (2014)
We reported a novel mono-β-cyclodextrin derivative, mono-6-deoxy-6-biguanidino-β-cyclodextrin (β-biGCD), which was investigated as a mimic of ADP/ATP carrier (AAC). Its affinity toward AMP, ADP, and ATP was evaluated by means of isothermal titration calorimetry (ITC). The association constants (Ka) of β-biGCD binding to AMP, ADP, and ATP were determined to be (1.07±0.04)×106, (5.86±0.02)×106, and (4.33±0.06)×10 6 L mol-1, respectively, which were 100-fold higher than mono-guanidino-β-cyclodextrin (ca. 104 L mol-1). UV spectroscopic titrations further confirmed the above results. The interaction between β-biGCD and nucleotides was probed by docking simulation. These results reveal that the biguanidinium moiety mimics the arginine residues of mitochondrial AAC protein.
6A-O-[(4-biphenylyl)acetyl]-alpha-, -beta-, and -gamma-cyclodextrins and 6A-deoxy-6A-[[(4-biphenylyl)acetyl]amino]-alpha-, -beta-, and -gamma-cyclodextrins: potential prodrugs for colon-specific delivery.
Uekama,Minami,Hirayama
, p. 2755 - 2761 (1997)
Cyclodextrins (CyDs) are known to be fermented to small saccharides by colonic microflora, whereas they are only slightly hydrolyzable and thus are not easily absorbed in the stomach and small intestine. This property of CyDs is particularly useful for colon-specific delivery of drugs. In this study, an antiinflammatory 4-biphenylylacetic acid (BPAA) was selectively conjugated onto one of the primary hydroxyl groups of alpha-, beta-, and gamma-CyDs through an ester or amide linkage, 6A-O-[(4-biphenylyl)acetyl[-alpha-, -beta-, and -gamma-CyDs (1-3) and 6A-deoxy-6A-[[(4-biphenylyl)acetyl]amino]-alpha-, -beta-, and -gamma-CyDs (4-6). In rat cecal and colonic contents (10%, w/v), 1 and 3 released more than 95% of BPAA within 1-2 h, and 2 released about 50% of the drug within 12 h. The amide prodrugs, 4-6, did not release BPAA in the cecal contents, but gave BPAA/maltose or BPAA/triose conjugates linked through an amide bond. On the other hand, these prodrugs were found to be stable in the contents of rat stomachs and small intestines, in intestinal or liver homogenates, and in rat blood. The serum levels of BPAA increased about 3 h after oral administration of 1 and 3 to rats, accompanying a marked increase in the serum levels, whereas 2 and 4-6 resulted in little increase of the serum levels. These facts suggest that BPAA is released after the ring opening of CyDs followed by the ester hydrolysis, and the BPAA activation takes place site-specifically in the cecum and colon. Therefore, the present CyD prodrug approach provides a versatile means of constructing a novel colon-specific drug delivery system.
Functionalization using biocompatible carboxylated cyclodextrins of iron-based nanoMIL-100
Ca?ón-Mancisidor, Walter,Carmona, Thais,Giménez-Marqués, Mónica,Gutiérrez-Cuti?o, Marlen,Hermosilla-Ibá?ez, Patricio,Mínguez Espallargas, Guillermo,Marco, José F.,Pérez, Edwin G.,Venegas-Yazigi, Diego
, (2021/10/21)
Here we report the first example of nanoMIL-100 particles modified with monomeric cyclodextrin derivatives of different length by exploiting strong interactions between non-saturated iron trimers at the external surface and carboxylate functionalities located at the end of biocompatible and flexible linkers of cyclodextrins. The main results revealed that, after the functionalization, the cyclodextrins are selectively located at the external surfaces covering the nanoparticles. Z potential measurements show that this functionalization induced changes respect to the bare nanoMIL-100 particles, however, the presence of the cyclodextrins does not modify the size neither porosity of the nanoparticles. The amount of cyclodextrins attached, investigated by thermogravimetry, increases with the length of the linker between CD cavity and nanoparticle surface, reaching up a 9 % wt. Auger spectroscopy suggested a clear predominant sp3 character after the functionalizations (vs. sp2 predominance in the unmodified nanoMIL-100). This study supposes the creation of an alternative family of hybrids based on carboxylated monomeric cyclodextrins.
