- Cholesterol-linked β-cyclodextrin - A thermotropic liquid-crystalline derivative
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Liquid-crystalline derivative of β-cyclodextrin (BCD) was prepared by covalent linking of monocholesteryl succinate (ChMS) with β-cyclodextrin. To the best of our knowledge, this was first ever attempt so far of its kind, in which BCD has been converted into its liquid-crystalline derivative through covalent linkage of a mesogen. The degree of substitution (DS) obtained was ≈2.00. The product was characterized by various techniques, such as FT-IR, NMR, DSC, hot-stage-coupled optical polarizing microscopy (OPM), microanalysis and chemical methods. Cholesterol-linked β-cyclodextrin (CDCh) derivative was found to exhibit thermotropic liquid-crystalline behavior. The product exhibited birefringence during first heating above 130°C, and it became isotropic at about 180°C, whereas the parent compound BCD decomposed without melting above 250 °C. A comparison of CDCh derivative to similar liquid-crystalline poly-saccharide derivatives is presented.
- Shaikh, Vasi Ahmed Ebrahim,Lonikar, Shrikant Vitthal,Dhobale, Deepa Arun,Pawar
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- A novel truncated basic fibroblast growth factor fragment-conjugated poly (ethylene glycol)-cholesterol amphiphilic polymeric drug delivery system for targeting to the FGFR-overexpressing tumor cells
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Targeted uptake of therapeutic nanoparticles in tumor cells-specific manner represents a potentially powerful technology in cancer therapy. In present study, we proposed a drug delivery system formulated with biocompatible and biodegradable cholesterol-block-poly (ethylene glycol) (Chol-PEG 2000-COOH) polymer. And the surface of the polymer was chemically linked with truncated bFGF fragments (tbFGF). The tbFGF could recognize fibroblast growth factor receptors (FGFR) that are highly expressed by a variety of human cancer cells. The micelles had a size distribution of about 10-50 nm and significantly enhanced the cytotoxicity of paclitaxel to LL/2 cells as demonstrated by MTT test (IC50 = 0.21 μg/mL for tbFGF conjugated Chol-PEG2000-COOH micelles (tbFGF-M-PTX) versus 26.43 μg/mL for free paclitaxel, respectively). Flow cytometry revealed the cellular uptake of rhodamine B encapsulated in the tbFGF-conjugated micelles was increased by 6.6-fold for HepG2, 6.2-fold for A549, 2.9-fold for C26 and 2.7-fold for LL/2 tumor cells, respectively, compared with micelles without tbFGF. The fluorescence spectroscopy images further demonstrated that the tbFGF conjugated micelles could specifically bind to the tumor cells that over-expressed FGFRs and then release rhodamine B into the cytoplasm. Our results suggest the tbFGF conjugated Chol-PEG2000-COOH micelles have great potential application for tumor targeting therapy.
- Cai, Lulu,Qiu, Neng,Li, Xia,Luo, Kaili,Chen, Xiang,Yang, Li,He, Gu,Wei, Yuquan,Chen, Lijuan
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- Poly(N-propargylamide)s bearing cholesteryl moieties: Preparation and optical activity
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We synthesized a novel chiral cholesteryl-based N-propargylamide (M ch, HCCCH2NHCOCH2CH2COOch, ch = cholesteryl) from which homopolymers [P(Mch)] with different molecular weights (number-average molecular weight: 8600, 14100 and 30000) were prepared. The polymers formed helical structures with a preferential helicity. The three polymers increased in both helix content and specific rotation as the molecular weight increased. P(Mch)-8600 was studied in detail as the model polymer. P(Mch)-8600 adopted helical conformations in toluene, THF, CHCl3 and CH2Cl2, exhibited thermal stability with a decomposition temperature of 273°C and formed a lyotropic liquid crystal under the studied conditions. Copolymers of different compositions of Mch and an achiral monomer (Met) were prepared. The copolymers formed helices to different degrees depending on the specific composition, indicating an effective approach for controlling the formation of helices in synthetic helical polymers.
- Zhang, Chaohong,Liu, Dong,Zhou, Bolin,Deng, Jianping,Yang, Wantai
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- Design and synthesis of new cholesterol-conjugated 5-fluorouracil: A novel potential delivery system for cancer treatment
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Cholesterol-conjugated 5-fluorouracil prodrugs were designed to be carried in vivo via low density lipoproteins (LDL) and subsequently undergo LDL-receptor-mediated internalisation into cancer cells. In vivo anti-cancer evaluation was performed using 5-fluorouracil-cholesterol conjugate in a mouse model. The obtained prodrugs were more potent than 5-fluorouracil control drug at the same 5-fluorouracil content (3 mg·kg-1).
- Radwan, Awwad A.,Alanazi, Fares K.
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- Matrix-molecule induced chiral enhancement effect of binary supramolecular liquid crystals
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Chiral enhancement effects associated with supramolecular liquid crystalline structures are studied, using a complex of achiral molecules (4,4′-bipyridine, 4Bpy) and chiral cholesteric liquid crystalline molecules (3-cholesteryloxycarbonylpropanoic acid, C4) as the model system. Non-mesogenic achiral molecule 4Bpy is used as the matrix element. The chiral enhancement of the supramolecular liquid crystalline structures can be revealed by circular dichroism (CD) and helical twisting power measurements. It is interesting that CD spectra of the complex exhibited an appreciably enhanced chiral property in comparison with that of the pure chiral cholesteric C4 molecules at room temperature. The helical pitch measurements by the Grandjean-Cano method also confirm the chiral enhancement effect. In addition, polarizing optical microscopy (POM) measurements indicate that the addition of matrix molecules leads to the explicit expression of the chiral liquid crystalline texture, i.e. twisted grain boundary (TGBA*) phase, at the liquid crystal temperature. Differential scanning calorimetry (DSC) and variable-temperature X-ray diffraction measurements further confirm the existence of the TGBA* phase. The binary supramolecular assembly structures are investigated by scanning tunneling microscope (STM) and the formation of hydrogen bonds between the chiral mesogens and the achiral matrix molecules can be directly observed. The variable-temperature Fourier transform infrared (FTIR) results further demonstrate that the hydrogen bonds persist until 168 °C. These results indicate that the introduction of a bifunctional aromatic base such as bipyridine could lead to self-assembled supramolecular architectures with discernible enhancements of chiral properties. The Royal Society of Chemistry.
- Ma, Xiao-Jing,Shen, Yong-Tao,Deng, Ke,Tang, Hong,Lei, Sheng-Bin,Wang, Chen,Yang, Yan-Lian,Feng, Xi-Zeng
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- Microtubes self-assembled from a cholesterol-modified nucleoside
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We describe the formation of lipid microtubes from a novel cholesterol-modified nucleoside in binary mixture with phospholipids. Stable cylindrical structures with an outer diameter of 2-3 μm and a length of 20-40 μm were formed. By varying the preparation conditions, thinner tubules with nanometre-scale diameters could also be obtained.
- Pescador, Paula,Brodersen, Nicolai,Scheidt, Holger A.,Loew, Martin,Holland, Gudrun,Bannert, Norbert,Liebscher, Juergen,Herrmann, Andreas,Huster, Daniel,Arbuzova, Anna
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- Synthesis of novel thiol-reactive amphiphilic lipids based on cholesterol for protein-liposome coupling
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The synthesis of a series of coupling lipids designed for covalently linking proteins to liposomes is described. The new compounds have in common a cholesterylsuccinyl unit as a lipid anchor and a thiol-reactive maleimidobenzoyl unit which are linked by alkyl or (poly)ethylene glycol spacers that differ in length and polarity.
- Kley, Joerg T.,Fichert, Thomas,Massing, Ulrich
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- Synthesis of cationic cholesterol derivatives with succinyl spacer group
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Syntheses of N, N, N-trimethyl [2-(3β-cholesteryloxy) syccinyloxyethyl] ammonium iodide, N,N-dimethyl-N-2-hydroxyethyl [2-(3β-cholesteryloxy)syccinyloxyethyl]ammonium iodide, and N-[(3β-cholesteryloxy)syccinyl]piperazine were performed. The compounds synthesized in a liposomal form may be used for delivery of genetical material into cells.
- Konstantinova,Klykov,Maslov,Serebrennikova
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- Synthesis of α-carboranyl-α-acyloxy-amides as potential BNCT agents
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Novel α-carboranyl-α-acyloxy-amides were prepared as potential BNCT agents utilizing three-component Passerini reaction. Preliminary cytotoxicity of the representative compounds on two brain tumor cell lines (U-87 and A-172) showed no effect on cell viability; an essential requirement for utility as potential BNCT agents.
- Jonnalagadda, Subash C.,Cruz, Jonathan S.,Connell, Ryan J.,Scott, Patricia M.,Mereddy, Venkatram R.
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- In-plane modulated smectic ? vs smectic 'A' lamellar structures in poly(ethyl or propyl ether imine) dendrimers
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A pair of first and second generation poly(alkyl ether imine) dendrimers is prepared, having covalently attached cholesteryl moieties at their peripheries. The pairs in each generation differ in the alkyl-linker which constitute the dendritic core moieties, even when the number of cholesteryl moieties remains uniform in each pair. The dendrimer pairs are two first and second generation poly(ethyl ether imine) and poly(propyl ether imine) dendrimers, modified with 4 and 8 cholesteryl esters at the peripheries in each pair, respectively. The dendrimer pairs exhibit differing thermotropic mesophase properties. Microscopic, thermal and X-ray diffraction studies reveal a lamellar mesophase for the first generation ethyl-, first and second generation propyl-linker dendrimers. Whereas, the second generation ethyl-linker dendrimer exhibits a layered structure with a superimposed in-plane modulation, the length of which corresponds to a rectangular column width. The role of the dendrimer core moieties with differing linkers in modifying the mesophase properties is studied.
- Kumar, Prabhat,Shankar Rao,Krishna Prasad,Jayaraman
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- Electrical conformational bistability of dimesogen molecules with a molecular chord structure
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Touching a chord: A field-dependent conformational change occurs in dimesogen molecules with flexible linking chains, which illustrates a molecular chord structure that is switchable by an electric field (see picture; HOPG = highly oriented pyrolytic graphite). No discernible changes are observed for dimesogen molecules with rigid linkers. (Figure Presented).
- Yang, Yan-Lian,Chan, Qi-Lin,Ma, Xiao-Jing,Deng, Ke,Shen, Yong-Tao,Feng, Xi-Zeng,Wang, Chen
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- Chitooligosaccharides Modified Reduction-Sensitive Liposomes: Enhanced Cytoplasmic Drug Delivery and Osteosarcomas-Tumor Inhibition in Animal Models
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Purpose: To investigate the potential of a reduction-sensitive and fusogenic liposomes, enabled by surface-coating with chotooligosaccharides (COS) via a disulfide linker, for tumor-targeted cytoplasmic drug delivery. Methods: COS (MW2000-5000) were chemically tethered onto the liposomes through a disulfide linker (-SS-) to cholesterol (Chol). Doxorubicin (DOX) was actively loaded in the liposomes. Their reduction-sensitivities, cellular uptake, cytotoxicity, pharmacokinetics and antitumor efficacy were investigated. Results: The Chol-SS-COS/DOX liposomes (100?nm) had zeta potential of 33.9?mV and high drug loading (13% w/w). The liposomes were stable with minimal drug leakage under physiological conditions but destabilized in the presence of reducing agents, dithiothreitol (DTT) or glutathione (GSH) at 10?mM, the cytosolic level. MTT assay revealed that the cationic Chol-SS-COS/DOX liposomes had higher cytotoxicity to MG63-osteosarcoma cells than non-reduction sensitive liposome (Chol-COS/DOX). Flow cytometry and confocal microscopy revealed that Chol-SS-COS/DOX internalized more efficiently than Chol-COS/DOX with more content to cytoplasm whereas Chol-COS/DOX located around the cell membrane. Chol-SS-COS/DOX preferentially internalized into MG63 cancer cell over LO2 normal liver cells. In rats both liposomes produced a prolonged half-life of DOX by 4 - 5.5 fold (p??0.001) compared with the DOX solution. Chol-SS-COS/DOX exhibited strong inhibitory effect on tumor growth in MG63 cell-bearing nude mice (n?=?6), and extended animal survival rate. Conclusions: Reduction-responsive Chol-SS-COS liposomes may be an excellent platform for cytoplasmic delivery of anticancer drugs. Conjugation of liposomes with COS enhanced tumor cell uptake, antitumor effect and survival rate in animal models.
- Yin, Xuelei,Chi, Yingying,Guo, Chuanyou,Feng, Shuaishuai,Liu, Jinhu,Sun, Kaoxiang,Wu, Zimei
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- Physico-chemical interactions of a new rod-coil-rod polymer with liposomal system: Approaches to applications in tryptophan-related therapies
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This work describes the synthesis of the new supramolecular rod-coil-rod polymer, designated as cholesterol-PEO1000-tryptophan (Chl-PEO-Trp), as well as its effects on the physico-chemical properties of phosphatidylcholine (PC)-based liposomes. The molecular interactions between the Chl-PEO-Trp and PC were characterized by HATR-FTIR, DSC, NMR, DLS and zeta (ζ) potential techniques. The Chl-PEO-Trp polymer yield was 75 %. FTIR and DSC data showed that the motion of almost all PC groups was restricted by the polymer, and it promoted a decrease of the trans-gauche isomerization of the PC methylene, restricting the mobility of the hydrophobic region of the liposomes. NMR analyses indicated a Chl-PEO-Trp-induced restriction in the rotation of the PC phosphorus and a discreet increase of the hydrogen mobility of the choline. Despite this increase in the rotation of the choline, DLS and ζ-potential analyses suggested a reorientation of the choline group toward the system surface, which contributed, along with the other physico-chemical effects, to a globally packed membrane arrangement and reduced liposome size. Data described in this work were correlated to possible applications of the Chl-PEO-Trp in its free or PC liposome-loaded forms in the diagnosis and therapy of cancer, SARS caused by coronaviruses, and central nervous system-related diseases.
- Cardoso dos Santos, Marinalva,Silva de Farias, Bruna,da Costa Cabrera, Diego,Roberto Sant'Anna Cadaval Junior, Tito,Antonio de Almeida Pinto, Luiz,Gon?alves Dal-Bó, Alexandre,de Lima, Vania Rodrigues
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- Liquid-crystalline compounds containing both a strong push-pull azo chromophore and a cholesteryl unit as photoresponsive molecular glass materials
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A series of liquid-crystalline (LC) compounds (R-Chol, R: CA, CN and NT), containing both a strong push-pull azo chromophore and a cholesteryl unit, was synthesized as novel molecular glass materials. The molecular structures and phases of the condensed state were characterized by spectral analyses, DSC, XRD and POM. The azo compounds existed as glassy solids at room temperature and entered the smectic LC phase above the glass transition temperature. Optical-quality solid films of R-Chol were obtained by spin-coating. The spin-coated films of CA-Chol and CN-Chol existed in the amorphous state and only the NT-Chol film showed weak birefringence and polydomain texture. Upon irradiation with a linearly polarized Ar+ laser (488 nm) beam, photoinduced orientation rapidly developed for CA-Chol and CN-Chol films, which showed significant photoinduced birefringence and dichroism. When the irradiating light was switched off, the birefringence did not show decay relaxation as is the usual case, but showed a small increase in the relaxation process. Photoinduced surface-relief-grating (SRG) formation was investigated by irradiating the films with two p-polarized interfering Ar+ laser beams. SRGs formed on the CA-Chol films showed the highest inscription rate in the series. The efficiencies of both photoinduced orientation and SRG formation were enhanced for the azo chromophore bearing the carboxylic group as the electron-withdrawing substituent. Two-dimensional (2D) quasi-crystal structures with 10- and 12-fold rotation symmetries were successfully fabricated on the CN-Chol films by using the dual-beam multiple exposure technique. The capability of the materials as photo-storage media was demonstrated by holographic recording.
- Wei, Renbo,Xu, Zeda,Liu, Xiyang,He, Yaning,Wang, Xiaogong
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- Cathepsin B-sensitive cholesteryl hemisuccinate-gemcitabine prodrug nanoparticles: Enhanced cellular uptake and intracellular drug controlled release
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Gemcitabine [2′,2′-difluoro-2′-deoxycytidine (dFdC)], firstline treatment for pancreatic cancer in the clinic, is a cytotoxic nucleoside analogue. Nucleoside transporters are required in the transport of gemcitabine into cells since it is a hydrophilic compound. Actually, there are significant drawbacks for the application of gemcitabine in clinic, including a short half-life and serious side effects. In order to overcome the mentioned drawbacks, a novel prodrug, cholesteryl hemisuccinate-gemcitabine (CHSdFdC), was synthesized through covalently coupling the amino group of gemcitabine with the carboxylic group of cholesteryl hemisuccinate. The amphiphilic prodrug self-assembled spontaneously as nanoparticles in aqueous media confirmed by transmission electron microscopy (TEM). Dynamic light scattering (DLS) measurement revealed that the mean particle size is approximately 200 nm in aqueous media. The CHSdFdC nanoparticles displayed accumulative controlled drug release in simulated lysosome conditions (pH 5.0 NaAc buffer solution containing cathepsin B); the amount of drug release reached up to 80% within 10 h. However, there was almost no drug release in pH 7.4 PBS and pH 5.0 NaAc buffer solutions without cathepsin B. All these results indicated the intracellularly controlled drug release manner of the CHSdFdC nanoparticles. The controlled release of dFdC from the CHSdFdC nanoparticles was related closely to cleavage of amide bonds by cathepsin B. The CHSdFdC nanoparticles exhibited increased ability to inhibit cell growth compared with gemcitabine in vitro. Meanwhile, the CHSdFdC nanoparticles exhibited enhanced cellular uptake ability against Bxpc-3 cells, and the amount of CHSdFdC was about 15 fold of gemcitabine during the 2.5 h incubation. All these results showed that the CHSdFdC nanoparticle prodrug has great potential in the treatment of pancreatic cancer.
- Xu, Yanyun,Geng, Jianqi,An, Ping,Xu, Yan,Huang, Jin,Lu, Wei,Liu, Shiyuan,Yu, Jiahui
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- Novel chitosan derivative for temperature and ultrasound dual-sensitive liposomal microbubble gel
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In this study, a novel liposome-loaded microbubble gel based on N-cholesteryl hemisuccinate-O-sulfate chitosan (NCHOSC) was designed. The structure of the NCHOSC was characterized by FTIR and 1H NMR. The liposomal microbubble gel based on NCHOSC with a high encapsulation efficiency of curcumin was formed and improved the solubility of curcumin. The diameter of most liposomal microbubble was about 950 nm. The temperature-sensitive CS/GP gel could be formulated at room temperature and would form a gel at body temperature. Simultaneously, the ultrasound-sensitive induced release of curcumin was 85% applying ultrasound. The results of cytotoxicity assay indicated that encapsulated curcumin in Cur-LM or Cur-LM-G was less toxic. The anti-tumor efficacy in vivo suggested that Cur-LM-G by ultrasound suppressed tumor growth most efficiently. These findings have shed some light on the potential NCHOSC material used to liposome-loaded microbubble gel for temperature and ultrasound dual-sensitive drug delivery.
- Chen, Daquan,Yu, Hongyun,Mu, Hongjie,Wei, Junhua,Song, Zhenkun,Shi, Hong,Liang, Rongcai,Sun, Kaoxiang,Liu, Wanhui
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- Chol-Dex nanomicelles: Synthesis, characterization and evaluation as efficient drug carriers for colon targeting
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Core-shell structures obtained from amphiphilic molecules on self-assembly in a medium have emerged as an important tool in the area of biomedical sciences. Here, we have synthesized cholesteryl-dextran (Chol-Dex) amphiphiles in sufficiently high yields via conjugation of cholesteryl hemisuccinate to dextran in two different concentrations (5 and 10%). After physicochemical and spectral analysis, the nanomicelles were subjected to size measurements. DLS and TEM confirmed the formation of core-shell type of nanomicelles. Hydrophobic drug-entrapped formulations (Metronidazole and Rifampicin) displayed sustained release behaviour of drugs from them. Sustained release at neutral pH demonstrated usefulness of the non-toxic delivery system for colon specific diseases.
- Goyal, Preeti,singh, Mahak,Kumar, Pradeep,Gupta, Alka
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- LHRHa aided liposomes targeting to human ovarian tumor cells: Preparation and cellular uptake
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In this study, a synthetic nonapeptide similar to luteinizing hormone-releasing hormone (LHRHa), the ligand of an extracellular membrane receptor specific to ovarian tumor cells, was selected as targeting moiety and electrically adsorbed to the negatively charged liposomes composed of phos-pholipid and monocholesterolsuccinate. Docetaxel, as the first line chemotherapy for ovarian tumor, was chosen to be encapsulated into the liposomes. And a high encapsulate efficiency (93%) and drug loading efficiency (20%) of liposomes were achieved via central composite design. In order to investigate the targeting efficiency of the drug delivery system, in vitro cell uptake was determined and the results showed an increasing uptake of LHRHa aided liposomes compared to normal ones.
- Yuan, Wen-Min,Song, Qin-Guo,Zhang, Zhi-Rong,Fu, Yao,Liu, Ji,He, Qin
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- Novel organogel harnessing Excited-State Intramolecular Proton Transfer process with aggregation induced emission and photochromism
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Two novel aggregation-induced emission compounds harnessing Excited-State Intramolecular Proton Transfer process based on salicylideneaniline derived from tetraphenylethylene and cholesterol moieties were synthesized and characterized. One of the compounds could gelate in cyclohexane exhibiting gelation-induced enhanced emission and the emission intensities can be reversibly changed with the gel-solution transition by alternate cooling and heating. Moreover, this compound showed photochromic behavior both in gel and solid states under UV light irradiation due to the loose packing of the molecules and permitting the molecule to rotate, which may be a potential candidate for external stimuli-responsive materials through tuning the self-assembly process of the functional gelator.
- Luo, Miao,Wang, Sheng,Wang, Meiling,Huang, Shaorong,Li, Chengpeng,Chen, Lin,Ma, Xiang
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- Preparation and application of brain glioma targeting berberine and folic acid modified lipid material
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The invention discloses preparation and application of a brain glioma targeting berberine and folic acid modified lipid material, and can be used for preparing lipidosome modified by brain glioma targeting Tween 80 coated berberine and folic acid. The liposome surface is coated with Tween 80 and can pass through the blood-brain barrier effectively through receptor-mediated endocytosis after binding with low density lipoprotein receptors to deliver the drug to the brain. In addition, the liposome uses folic acid and berberine to modify brain glioma targeting and mitochondrial targeting capacity of the liposome, and the long chain of polyethylene glycol is introduced to stabilize the liposome. A new thought and a method can be provided for targeted therapy of glioma, and a wide application prospect is provided. pH MDR. The utility model can provide a new idea and a method for targeted therapy of brain glioma.
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Paragraph 0009; 0018
(2021/09/21)
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- MONOSACCHARIDE-TAGGED NANO-LIPOSOME DRUG DELIVERY SYSTEM, THE MANUFACTURE AND USE FOR DRUG TARGETING DELIVERY THEREOF
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The present invention relates to a monosaccharide-tagged nano-liposome, which is characterized that the targeting monosaccharide is conjugated to cholesterol and the monosaccharide-conjugated cholesterol is incorporate into the phospholipid bilayer. The nano-liposome of present invention exhibits the ability to carry the loaded drug to target cells, such as cancer cells and cancer stem cells in a tumor tissue, and be internalized by endocytosis to produce direct cytotoxicity or suppress stemness gene expression, so as to avoid toxicity to normal cells and effectively improve the therapeutic effect of cancer clinical medication and radiation therapy.
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Paragraph 0026
(2021/03/27)
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- Folic acid modified liposome complex and its preparation and use (by machine translation)
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The present invention relates to folic acid modified liposome complex and its preparation and use, which belongs to the field of medicine. The present invention provides folic acid modified liposome complex, it is composed of the following weight proportion of the raw materials with the: loaded with the BIM - S gene recombinant expression vector 1 parts, folic acid modified liposome 5 more than, wherein said folic acid is modified liposome comprising (2, 3 - dioleoyl - propyl) - trimethylamine, cholesterol, polyethylene glycol - succinimide - cholesterol and folic acid - polyethylene glycol - succinimide - cholesterol prepared of raw materials. The invention also provides the liposome method for preparing the compound and use thereof. The present invention provides of the folic acid modified liposome composition not only can kill the lung cancer cell, can also be through targeting TAM to influence the tumor micro-environment, for clinical treatment of lung cancer provides a new choice of drug use for. (by machine translation)
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Paragraph 0049; 0055; 0056
(2019/06/30)
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- Chloroquine cholesterol derivative and its preparation and use (by machine translation)
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The invention belongs to the field of chemical medicine, in particular to chloroquine derivative and its preparation and use. The present invention provides a kind of chloroquine derivatives, its structure is shown as formula I. The invention also provides the above-mentioned chloroquine cholesterol derivative of the preparation method and use thereof. The present invention provides of the chloroquine cholesterol derivatives can effectively inhibit the RAT fibroblast proliferation, and can be effective in the treatment of pulmonary fibrosis, and can produce the anti-inflammatory effect, for the preparation of anti-fibrotic, anti-inflammatory and anti-tumor drug provides a new selection. (by machine translation)
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Paragraph 0033; 0035
(2018/09/11)
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- Copper-free catalytic click chemical module molecule and application of copper-free catalytic click chemical module molecule in medicine
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The invention relates to the field of chemistry and a preparation, and more specifically relates to preparation of a copper-free catalytic click chemical module molecule and an application of the copper-free catalytic click chemical module molecule in construction of a drug delivery carrier and surface multifunctional modification. According to the invention, a cyclooctyne derivative and a liposome matrix are used for forming stable liposome through a dispersing method; a physical effect is used for efficiently loading the gene treatment medicines or chemotherapeutics, furthermore, the stable drug liposome is formed; finally, through a click chemical reaction of copper-free catalysis, and the azide derivatives having different functions are modified to the surface of the drug liposome according to the requirement and the formation of a chemical bond. The method can avoid the toxicity of heavy metal copper ions, and overcomes the disadvantages of DNA degradation and protein denaturation brought by copper catalysis. Under condition that efficient and stable medicine carrying is guaranteed, the construction of the multifunctional drug delivery carrier with safety, stabilization and high efficiency can be obtained.
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Paragraph 0100
(2017/08/28)
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- New amphiphilic polycarbonates with side functionalized cholesteryl groups as biomesogenic units: synthesis, structure and liquid crystal behavior
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The synthesis of four new amphipathic copolymers with side functionalized-cholesterol based aliphatic polycarbonates is described through the ring-opening polymerization and coupling reaction. The chemical structures, liquid crystal (LC) behavior, and thermal stability of the chiral monomers and copolymers obtained in this study were characterized using Fourier transform infrared (FT-IR) spectroscopy, proton nuclear magnetic resonance (1H NMR) spectroscopy, gel permeation chromatography (GPC), polarizing optical microscopy (POM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and thermogravimetric analysis (TGA) measurements. The effect of the spacer length on the molecular interaction and mesophase of the chiral monomers and copolymers was investigated. It was found that chiral monomers with longer spacer seemed beneficial for the formation of mesophases, and the additional ordering on polymerization caused mesophases to be more ordered than for the corresponding monomers. The LC copolymers all revealed a smectic A phase with an interdigitated molecular arrangement. The results seemed to show a decreased tendency toward the glass transition temperature, and isotropic temperature for the LC copolymers by increasing the spacer length. In addition, four LC copolymers had a good thermal stability.
- Xu, Xiaoxu,Liu, Xiaofeng,Li, Qun,Hu, Jianshe,Chen, Qifan,Yang, Liqun,Lu, Yanhua
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p. 14176 - 14185
(2017/03/11)
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- Posaconazole derivative, synthesis and application in prolonged action preparation thereof
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The invention relates to a posaconazole derivative, synthesis and an application in a prolonged action thereof. The invention relates to a formula of a compound and salt, N-oxide, quaternary ammonium and stereoisomer of the compound, wherein R1-R8 are defined according to what is claimed. The invention also relates to a preparation formula of an intermediate body and a method of the compound. The invention further relates to a formula of an application of the compound as a drug, especially the application in preventing or treating fungal infection. The detailed formulas are in the specification.
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Paragraph 0091
(2017/04/03)
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- A thienopyridine derivative and its preparation and use (by machine translation)
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The invention relates to a thienopyridine derivative and its preparation and use, the invention the thienopyridine derivatives have the following formula (I) indicated by the structure, wherein the R1 , R2 , R3 And R4 According to the defined in the claims, the invention also comprises formula (I) preparation method of the compound, a pharmaceutically acceptable salt thereof, compound solvent, polymorphism body, enantiomer or a racemic mixture, pharmaceutical compositions containing them and their use as medicaments, in particular for the prevention or treatment of atherosclerosis disease, myocardial infarction, stroke, ischemic cerebral thrombosis, peripheral artery disease, acute coronary syndrome or coronary intervention postoperative thrombosis. (by machine translation)
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Paragraph 0040
(2017/08/19)
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- CELLULAR SIGNALLING INHIBITORS, THEIR FORMULATIONS AND METHODS THEREOF
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The present disclosure relates generally to Cellular Signalling inhibitors of compound of Formula (I), compositions and formulations comprising the same, methods, processes, and uses thereof. In particular, the present disclosure provides CSF-1R inhibitors demonstrating sustained inhibition of CSF/CSF1R signalling pathway with decreased toxicity. The present disclosure also provides supramolecular combinatorial therapeutics, wherein a CSF-1R inhibitor is combined with one or more of a chemotherapeutic agent, a kinase inhibitor, and an immunoregulator, each of which is optionally conjugated with a lipid. The present disclosure also provides a method for treating cancer, allergy, Systemic lupus erythematosus, nephritis, Chronic Obstructive Pulmonary Disease, and abnormal macrophage functions or any combinations thereof.
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Paragraph 00195
(2017/09/05)
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- Anionic lipids and lipid nano-structures and methods of producing and using same
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Anionic non-phospholipids, as well as lipid nanostructures formed therefrom, are disclosed herein. Also disclosed are methods of producing and using same.
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Page/Page column 12
(2015/11/27)
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- Study on the controlled gel formation and photochromic properties of a new cholesterol-bridge-naphthopyran dyad
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A cholesterol-bridge-naphthopyran dyad (NP-MCB) was designed and synthesized. NP-MCB can readily selfassemble into gels under ultrasound-radiation in several organic solvents and the formed gels easily transfer to solution by heat. This reversible process can be repeated many times. Scanning Electron Microscopy results showed that the morphologies of all formed xerogels in different solvents have fibrillar microstructure. The gels formation was due to energy and pressure afforded by the ultrasonic process, resulting in formation of molecular hydrogen bonding and molecular aggregation. NP-MCB displayed the normal photochromism both in solution and gel states. The kinetic results confirm that the colored merocyanine in gels show a slower fading speed than that in solution due to the compact aggregation of NP-MCB molecules in gels. The xerogel film formed in polar gelling solvent had large surface wettability than that in nonpolar gelling solvent.
- Sun, Lin,Wang, Guang,Liu, Longbo,Wang, Ai Xia
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p. 1343 - 1348
(2014/06/09)
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- Structure-Based Rational Design of Prodrugs to Enable Their Combination with Polymeric Nanoparticle Delivery Platforms for Enhanced Antitumor Efficacy
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Drug-loaded nanoparticles (NPs) are of particular interest for efficient cancer therapy due to their improved drug delivery and therapeutic index in various types of cancer. However, the encapsulation of many chemotherapeutics into delivery NPs is often hampered by their unfavorable physicochemical properties. Here, we employed a drug reform strategy to construct a small library of SN-38 (7-ethyl-10-hydroxycamptothecin)-derived prodrugs, in which the phenolate group was modified with a variety of hydrophobic moieties. This esterification fine-tuned the polarity of the SN-38 molecule and enhanced the lipophilicity of the formed prodrugs, thereby inducing their self-assembly into biodegradable poly(ethylene glycol)-block-poly(d,l-lactic acid) (PEG-PLA) nanoparticulate structures. Our strategy combining the rational engineering of prodrugs with the pre-eminent features of conventionally used polymeric materials should open new avenues for designing more potent drug delivery systems as a therapeutic modality.
- Wang, Hangxiang,Xie, Haiyang,Wu, Jiaping,Wei, Xuyong,Zhou, Lin,Xu, Xiao,Zheng, Shusen
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supporting information
p. 11532 - 11537
(2016/02/19)
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- OLIGOMER-CONTAINED NANOPARTICLE COMPLEX RELEASE SYSTEM
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An oligomer-contained nanoparticle complex is provided. The oligomer-contained nanoparticle complex of the invention comprises (a) a nanoparticle, (b) a polymer with high molecule weigh, (c) a target molecule, (d) an oligomer, wherein the oligomer is crosslinked with the polymer by the intermolecular hydrogen bonds or electron bonds, and e) a space for active substances, wherein the space for active substances is encapsulated by the nanoparticle. The oligomer-contained nanoparticle complex of the invention has the high stability and fast drug release rate, and would not be largely accumulated in normal tissues. The invention also provides a method for preparing the oligomer-contained nanoparticle complex and the method for releasing drug.
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Paragraph 0070; 0071
(2015/01/06)
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- Amides derived from heteroaromatic amines and selected steryl hemiesters
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The current interest of the team has been focused on investigation of novel amides with potential cytotoxicity. The presented series of compounds was synthesized from selected steryl hemiesters and heteroaromatic amines. The synthetic protocol was designed in a simple and economic way, and divided into several general methodologies applicable to the compounds synthesized. The cytotoxicity was tested on cells derived from human T-lymphoblastic leukemia, breast adenocarcinoma and cervical cancer, and compared with tests on normal human fibroblasts. Most of the lanosterol-based compounds (3-5 and 7-10) showed medium to good cytotoxicity, while only two derivatives of cholesterol (18 and 19) showed medium cytotoxicity on human T-lymphoblastic leukemia cell line. The compounds 8 and 9 displayed the reasonable cytotoxicity among this series of amides, tested on the cell lines of T-lymphoblastic leukemia [14.5 ± 0.4 μM (8) and 18.5 ± 3.9 μM (9)], breast adenocarcinoma [19.5 ± 2.1 μM (8) and 23.1 ± 4.0 μM (9)] and cervical cancer [24.8 ± 5.3 μM (8) and 29.1 ± 4.7 μM (9)]. Only the compound 8 was adequately less active on normal human fibroblasts (40.4 ± 11.1 μM).
- Bildziukevich, Uladzimir,Rárová, Lucie,?aman, David,Havlí?ek, Libor,Dra?ar, Pavel,Wimmer, Zdeněk
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p. 1347 - 1352
(2013/12/04)
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- Photoresponsive diblock copolymers bearing strong push-pull azo chromophores and cholesteryl groups
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A series of diblock copolymers bearing strong push-pull azo chromophores and cholesteryl groups on the respective blocks was synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization. The liquid crystal phase structure, microphase-separated morphology, and photoresponsive properties of the block copolymers were investigated by using DSC, POM, AFM, XRD and laser irradiation. The results show that the cholesteryl block (PChEMA) forms smectic-A mesophase and the morphology depends on the length of the azo block (PAzoCN). When the azo block is short, such as PChEMA50-b-PAzoCN 7, no microphase separation can be identified. For PChEMA 50-b-PAzoCN28, PAzoCN appears as the hexagonal-packed nanocylinders embedded in the PChEMA matrix. When the azo block length further increases, the block copolymer PChEMA50-b-PAzoCN73 forms microphase-separated lamellae. The microphase separation shows no obvious restraint on the photoinduced orientation of the azo chromophores, but micron-scale mass transport of the photoresponsive PAzoCN block is inhibited by the phase confinement.
- Zhu, Yu,Zhou, Yuqi,Chen, Zhen,Lin, Ran,Wang, Xiaogong
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scheme or table
p. 3566 - 3576
(2012/09/07)
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- Sterols as anticancer agents: Synthesis of ring-B oxygenated steroids, cytotoxic profile, and comprehensive SAR analysis
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The cytotoxicity of oxysterols was systematically studied in tumor and normal cells. Synthetic strategies to prepare this library included oxidations at ring B and a new method to yield 6β-hemiphthalates directly from Δ5-steroids. Most oxysterols were cytotoxic and showed selectivity toward cancer cells, LAMA-84 cells (leukemia) being particularly sensitive to 4, 8, 22, and 27 (IC50 5.6 μM). The structural requirements to induce selective toxicity are discussed to shed light on the development of new anticancer drugs.
- Carvalho, Jo?o F. S.,Silva, M. Manuel Cruz,Moreira, Jo?o N.,Sim?es, Sérgio,Sá E Melo, M. Luisa
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supporting information; experimental part
p. 7632 - 7638
(2011/02/21)
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- FOSFLUCONAZOLE DERIVATIVES, SYNTHESIS, AND USE IN LONG ACTING FORMULATIONS
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The invention relates to a compound of formula (I) and the salts, N-oxides, quaternary amines, and stereoisomers thereof, wherein R1 to R8 are as defined in the claims. The invention further relates to intermediates and methods for the preparation of the compounds of formula (I). The invention also relates to the compounds of formula (I) for use as a medicament, particularly for the prevention or treatment of fungal infections.
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Page/Page column 31-33
(2010/10/03)
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- Development of glycyrrhetinic acid-modified stealth cationic liposomes for gene delivery
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The glycyrrhetinic acid-modified stealth cationic liposomes (GA-PEG-CLs) loaded with pDNA (GA-PEG-CLPs) were developed and found to transfect human hepatocellular carcinoma cell line HepG2 with high efficiency. GA-PEG-CLs were comprised of DOTAP, cholesterol (Chol) and glycyrrhetinic acid-polyethyleneglycol-cholesterol conjugate (GA-PEG-Chol). Agarose gel electrophoresis revealed that 5% GA-PEG-CLs constituted by DOTAP/Chol/GA-PEG-Chol at molar ratio of 50:45:5 could completely entrap pDNA at a lower liposomes/pDNA weight ratios of 4:1 (N/P ratio: 1.14). Compared to ordinary cationic liposomes (CLs), steric cationic liposomes (PEG-CLs) and 1% GA-PEG-CLs made from DOTAP/Chol/MPEG2000-Chol/GA-PEG-Chol at molar ratio of 50:45:4:1, 5% GA-PEG-CLs were found to possess the highest transfection efficiency as gene vectors in serum-free or serum-containing medium in PKCα over-expressed HepG2 cells but no significance difference in human embryonic kidney cell line HEK 293. Additionally, 5% GA-PEG-CLs have the lowest cytotoxicity on human normal hepatocyte cell line L02. The competitive inhibition experiments mediated by GA were carried out in HepG2 cells, which demonstrated that GA-PEG-CLs could deliver selectively pDNA to hepatoma cells by the targeting moiety GA. In conclusion, GA-PEG-CLs containing 5% GA-PEG-Chol might be one of the most potential gene vectors as hepatoma targeting therapy.
- He, Zhi Yao,Zheng, Xi,Wu, Xiao Hua,Song, Xiang Rong,He, Gu,Wu, Wen Fang,Yu, Shui,Mao, Sheng Jun,Wei, Yu Quan
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experimental part
p. 147 - 154
(2011/12/03)
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- A new class of star-shaped cholesteric liquid crystal containing a 1,3,5-trihydroxybenzene unit as a core
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A new class of star-shaped cholesteric liquid crystals were designed and synthesized, which used 1,3,5-trihydroxybenzene unit as a core and ω-cholesteric alkyl diacid monoester as mesogenic arm. Their chemical structures were confirmed by element analyses, FT-IR, and 1H NMR. The mesomorphic properties and thermal stability were investigated by differential scanning calorimetry, thermogravimetric analysis, polarizing optical microscopy, and X-ray diffraction measurements. The experimental results demonstrated that the mesogenic arm structures strongly affected the phase behavior. 4a did not show any liquid crystallinity, while 4b, 4c and 4d revealed reversible cholesteric phase transition. As the intermedius alkyl chain of the star-shaped compounds lengthened (from n = 2 to n = 8), their melting points decreased but mesomorphic temperature ranges increased. Focal conic texture, one of cholesteric phase can be observed in the liquid crystalline state.
- Yao, Dan-Shu,Zhang, Bao-Yan,Zhang, Wei-Wei,Tian, Mei
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- METHODS AND COMPOSITIONS FOR THE EFFICIENT DELIVERY OF THERAPEUTIC AGENTS TO CELLS AND ANIMALS
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The present invention provides methods of carrying out the safe and reliable preparation of lipids comprising quaternary amines. Such lipids are especially suited for introducing therapeutic agents into cells or organisms. In particular, the lipids of the invention are suitable for the efficient transfer of gene therapy agents into mammalian cells or organisms in a cell type specific or tissue specific manner.
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Page/Page column 55
(2008/06/13)
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- Functional organogel based on a salicylideneaniline derivative with enhanced fluorescence emission and photochromism
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A new organogelator based on a salicylideneaniline derivative with cholesterol moieties was synthesized, and it was proposed that it could gelate various organic solvents, such as 1-butanol, 1-octanol, butyl acetate, tetrachloromethane, benzene, toluene through combination with a gelation test. From the results of analysis by UV/Vis absorption, circular dichroism (CD), X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) studies and semiempirical (AMI) calculations, we believed that the gelator molecules could self-assemble into left-handed helical nanofibers through unimolecular layer packing, which further twisted into the thicker fibers and constructed 3D networks in the gel phase. Interestingly, the organogel exhibited strong fluorescence enhancement relative to a solution of the same concentration because of the formation of J aggregations. Meanwhile, photochromism of the organogel could take place under UV-light irradiation. Both strong fluorescence emission and photochromism properties were concurrent in one system based on a salicylideneaniline derivative. It was suggested that the self-assembly of the functional organogelator could lead to unique photophysical properties.
- Xue, Pengchong,Lu, Ran,Chen, Guojun,Zhang, Yuan,Nomoto, Hiroyuki,Takafuji, Makoto,Ihara, Hirotaka
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p. 8231 - 8239
(2008/09/16)
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- Amphiphilic block copolymer and polymeric composition comprising the same for drug delivery
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The present invention relates to an amphiphilic block copolymer of a hydrophilic block and a hydrophobic block with a terminal hydroxyl group wherein the terminal hydroxyl group of the hydrophobic bock is substituted with a tocopherol or cholesterol group. It also relates to polymeric compositions capable of forming stable micelles in an aqueous solution, comprising the amphiphilic block copolymer and a polylactic acid derivative wherein one or more ends of the polylactic acid are covalently bound to at least one carboxyl group.
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Page/Page column 15
(2010/02/13)
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- Novel cationic amphiphiles
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A cationic amphiphile for facilitating transport of a biologically active molecule into a cell has the structure A-F-D, in which A is a lipid anchor, D is a head group, and F is a spacer group having the structure described herein. A method for facilitating transport of a biologically active molecule into a cell comprises preparing a lipid mixture comprising a cationic amphiphile having structure A-F-D, preparing a lipoplex by contacting the lipid mixture with a biologically active molecule; and contacting the lipoplex with a cell, thereby facilitating transport of the biologically active molecule into the cell.
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Page/Page column 38, 7
(2010/02/06)
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- Synthesis and transfection properties of novel non-toxic monocationic lipids. Variation of lipid anchor, spacer and head group structure
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This report describes the synthesis and the transfection properties of novel monocationic non-toxic lipids. We have carried out structural variations in all three units of the transfection lipid, the lipid anchor, the spacer moiety and the positively charged head group. Our results lead to the conclusion that systematic modification of structural subunits is a promising way to enhance the transfection efficiency. (C) 2000 Elsevier Science Ltd. All rights reserved.
- Fichert, Thomas,Regelin, Anne,Massing, Ulrich
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p. 787 - 791
(2007/10/03)
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- Synthesis and orally macrofilaricidal evaluation of niclosamide lymphotropic prodrugs
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The development of new macrofilaricidal drugs is described following a strategy for the promotion of the lymphatic transport of anthelminthic drugs by-passing the liver. The selected compound was niclosamide (CAS 50-65-7) which is very effective in vitro against infective larvae but has no significant antifilarial activity when orally administered at 200 μmol/kg. To estimate the interest of such an approach, the synthesis of 5 prodrugs was achieved in a first stage. The intrinsic antifilarial activity and the delayed effect of these compounds were evaluated in vitro. Then, in vivo tests were performed with Molinema dessetae infective larvae to select the best ligands. The prodrug V 1,3-dihexadecanamido-2-[4-chloro(2-chloro-4-nitroanilinocarbonyl)pheny loxy-carbonylpropanoyloxy]propane (having a diamide function) was responsible for an in vitro delayed effect and an orally in vivo activity (200 μmol/kg when administered in a single dose). The biological improvement of this easily micellizable prodrug which is stable to intestinal enzymes in respect to Niclosamide confirms such a strategy.
- ElKihel,Loiseau,Bourass,Gayral,Letourneux
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p. 1259 - 1264
(2007/10/02)
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- NEW METHOD OF PREPARATION OF CARDIOGLYCOSIDE HEMISUCCINATES
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An indirect method for preparation of hemisuccinates (hydrogen butanedioates) is described, consisting in reaction of hydroxy derivatives with 2-(trimethylsilyl)ethyl hemisuccinate (I), followed by removal of the 2-(trimethylsilyl)ethyl group from the mixed succinate with tetrabutylammonium fluoride.It has been applied to the synthesis of hemisuccinates derived from cholesterol (II), (20E)-21-methoxycarbonylpregna-5,20-dien-3β-ol (V), digitoxigenin (XII), digitoxin (XV) and digoxin (XVIII).The method, however, is not suitable for the preparation of estrone hemisuccinate X which is cleaved with tetrabutylammonium fluoride to give estrone (VIII).
- Pouzar, Vladimir,Cerny, Ivan,Drasar, Pavel,Havel, Miroslav
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p. 2019 - 2028
(2007/10/02)
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- A NOVEL PREPARATION OF HEMISUCCINATES
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Hemisuccinates are prepared by condensation of succinic acid mono-2-(trimethylsilyl)ethyl ester with alcohols and subsequent aprotic removal of the protective group.
- Pouzar, Vladimir,Drasar, Pavel,Cerny, Ivan,Havel, Miroslav
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p. 501 - 507
(2007/10/02)
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