- Syntheses of deuterium-labelled cholesteryl neoglycolipids
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Four deuterium-labelled neoglycolipids derived from cholesterol were synthesized for embedment into liposomes. Deuterium atoms were either incorporated by CH2 replacement with a CD2 group in the triethylene glycol spacer arm between the cholesteryl residue and the sugar moiety (products 2-4) or incorporated directly on the acetamido function in the sugar head (compound 5). Copyright
- Lafont, Dominique,Boullanger, Paul,Gambetta, Antoine
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Read Online
- Apoptosis inducing properties of 3-biotinylate-6-benzimidazole B-nor-cholesterol analogues
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In this work, a series of Biotin-substituted B-nor-cholesteryl benzimidazole compounds were synthesized. The antiproliferative activities of these compounds were evaluated in vitro using a series of human cancer cell lines, including HeLa (cervical cancer), SKOV3 (ovarian cancer), T-47D (thymus gland cancer), MCF-7 (human breast cancer) and HEK293T (normal renal epithelial) cells. These compounds displayed distinct antiproliferative activities against the currently tested cancer cells. The apoptotic properties induced by compound 6d were further investigated. Our results showed that compound 6d could induce the apoptosis of SKOV3 cells, blocking the cell growth in S-phase. Western blotting analyses revealed that compound 6d can induce cell apoptosis via the mitochondria-dependent pathway.
- Zhu, Zhiling,Liu, Zhiping,Cui, Jianguo,Huang, Yanmin,Chen, Hualong,Wu, Yulan,Huang, Xiaotong,Gan, Chunfang
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Read Online
- LIPIDIC ANALOGS OF ANTI-CANCER STEM CELL AGENT
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A group of specific sulfated flavonoid agents carrying cholesterol modification display promising in vivo anti-cancer activity through selective inhibition of cancer stem cells, and not of adult or hematopoietic stem cells. The compounds exhibit high potency, excellent oral bioavailability and a physiologically relevant therapeutic window.
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Page/Page column 12; 34; 35
(2020/09/19)
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- Self-organization of cholesterol-side-chain liquid crystalline polymers by tailoring the main chain structure and flexible spacer length
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Three kinds of side-chain liquid crystalline polymers (SCLCPs), in which cholesteryl mesogens (Chol) were linked to polyacrylate (PCholAC-m), polymethacrylate (PCholMC-m), and poly(2-vinylbenzene-1,4-dioate) (PCholVA-m) backbones through methylene spacers of different lengths (m = 0, 2, 4, 6, 8, and 10), were successfully synthesized using free-radical polymerization. The phase behavior and structure of the polymers were investigated in detail using DSC, POM, and SAXS. The results indicated that the Chol-SCLCPs displayed interesting self-organization by varying the main-chain structure and spacer length. The polymers initially form a smectic A phase, except for PCholAC-0 without a liquid crystalline phase. Next, polymers PCholAC-m (m = 2, 4, 6) formed a two-layer smectic A phase in which the alkyl tail was overlapped (SmA2). Two-phase coexisting structures were observed in PCholAC-m (m = 8, 10), including a bilayer smectic A phase in which the alkyl tail was inserted into the mesogens (SmAd) and a single-layer smectic A phase in which the mesogens were overlapped (SmA1). Similar results were observed for PCholMC-m. Furthermore, PCholMC-0 possessed a stable bilayer SmA2 owing to the methyl steric effect of the main chain. PCholVA-m (m = 0, 2, 4) samples showed a well-defined smectic A phase in which the backbone was squeezed by the parallel side chains on both sides. PCholVA-6 and PCholVA-10 exhibited a SmAd phase. The two-phase coexisting structures were also found in PCholVA-8. Finally, the glass transition temperature of the polymers decreased with increasing flexible spacer length because the flexible spacer acted as an internal plasticizer in the system. However, changes in the polymer clearing points demonstrated the diversity resulting from the different smectic A phase structures.
- Yang, Xiwen,Chen, Shaonan,Luo, Hang,Xu, Haoran,Chen, Sheng
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p. 5429 - 5440
(2019/04/04)
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- 3-biotin ether ester-B reduction-cholesteric benzimidazole compound and preparation method and application thereof
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The invention discloses a 3-biotin ether ester-B reduction-cholesteric benzimidazole compound and a preparation method and application thereof. The 3-biotin ether ester-B reduction-cholesteric benzimidazole compound is characterized in that the chemical structure formula refers to the description, wherein n is an even number which is more than or equal to 2; R1 is H or CH3; R2 is H or OCH3. The 3-biotin ether ester-B reduction-cholesteric benzimidazole compound is obvious in effect on inhibiting cells of various tumor cell strains such as human uterine cervix cancer cell strains, ovarian carcinoma cell strains and human breast carcinoma cell lines; and meanwhile, the 3-biotin ether ester-B reduction-cholesteric benzimidazole compound is nontoxic to human renal epithelial cells and can be applicable to preparation of drugs for treating cancers.
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Paragraph 0043; 0048; 0052; 0057
(2019/01/16)
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- Catalytic cyclometallation in steroid chemistry VI: Targeted synthesis of hybrid molecules based on steroids and tetradeca-5Z,9Z-diene-1,14-dicarboxylic acid and study of their antitumor activity
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Hybrid molecules based on a number of steroids (cholesterol, pregnenolone, androsterone) and 1,14-tetradeca-5Z,9Z-dienedicarboxylic acid linked via mono- and diethylene glycol spacers were synthesized for the first time and studied for antitumor activity in vitro. The acid was prepared using catalytic cyclomagnesiation of oxygenated 1,2-dienes with Grignard reagent in the presence of Cp2TiCl2 as the key synthetic step. Using flow cytometry, the new molecules were shown for the first time to be efficient apoptosis inducers in the HeLa, Hek293, U937, Jurkat, and K562 cell cultures and to have dose-dependent effect on the S and G2 phases of the cell cycle.
- D'yakonov, Vladimir A.,Tuktarova, Regina A.,Dzhemileva, Lilya U.,Ishmukhametova, Svetlana R.,Yunusbaeva, Milyausha M.,Dzhemilev, Usein M.
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- FLUORESCENT ANTICANCER PLATINUM DRUGS
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The present disclosure is in relation to the field of nanotechnology and cancer therapeutics. In particular, the present disclosure relates to fluorescent platinum based compounds. The disclosure further relates to synthesis of said fluorescent platinum based compounds, nanoparticles and compositions comprising said fluorescent platinum based compounds/nanoparticles. The disclosure also relates to methods of managing cancer by the fluorescence changes between aforesaid platinum based compounds and corresponding free ligands, nanoparticles and compositions.
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Paragraph 0463
(2018/11/21)
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- Hybrid Lipids Inspired by Extremophiles and Eukaryotes Afford Serum-Stable Membranes with Low Leakage
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This paper presents a new hybrid lipid that fuses the ideas of molecular tethering of lipid tails used by archaea and the integration of cholesterol groups used by eukaryotes, thereby leveraging two strategies employed by nature to increase lipid packing
- Koyanagi, Takaoki,Cao, Kevin J.,Leriche, Geoffray,Onofrei, David,Holland, Gregory P.,Mayer, Michael,Sept, David,Yang, Jerry
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supporting information
p. 6757 - 6762
(2017/05/29)
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- BIPOLAR TETRAETHER LIPIDS
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Disclosed herein, inter alia, are compounds, compositions, and liposomes and methods of thereof.
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Paragraph 0034; 0569; 0570
(2017/03/21)
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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 00183
(2017/09/05)
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- Generation of Alkoxyl Radicals by Photoredox Catalysis Enables Selective C(sp3)-H Functionalization under Mild Reaction Conditions
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Reported herein is the first visible-light-induced formation of alkoxyl radicals from N-alkoxyphthalimides, and the Hantzsch ester as the reductant is crucial for the reaction. The selective hydrogen atom abstraction by the alkoxyl radical enables C(sp3)-H allylation and alkenylation reactions under mild reaction conditions at room temperature. Broad substrate variations, including a structurally complexed steroid, undergo the C(sp3)-H functionalization reaction effectively with high regio- and chemoselectivity.
- Zhang, Jing,Li, Yang,Zhang, Fuyuan,Hu, Chenchen,Chen, Yiyun
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supporting information
p. 1872 - 1875
(2016/02/03)
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- SILENCING OF POLO-LIKE KINASE EXPRESSION USING INTERFERING RNA
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The present invention provides compositions comprising interfering RNA (e.g., siRNA, aiRNA, miRNA) that target polo-like kinase 1 (PLK-1) expression and methods of using such compositions to silence PLK-1 expression. More particularly, the present invention provides unmodified and chemically modified interfering RNA molecules which silence PLK-1 expression and methods of use thereof. The present invention also provides serum-stable nucleic acid-lipid particles (e.g., SNALP) comprising an interfering RNA molecule described herein, a cationic lipid, and a non-cationic lipid, which can further comprise a conjugated lipid that inhibits aggregation of particles. The present invention further provides methods of silencing PLK-1 gene expression by administering an interfering RNA molecule described herein to a mammalian subject. The present invention additionally provides methods of identifying and/or modifying PLK-1 interfering RNA having immunostimulatory properties. Methods for sensitizing a cell such as a cancer cell to the effects of a chemotherapy drug comprising sequentially delivering PLK-1 interfering RNA followed by the chemotherapy drug are also provided.
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Paragraph 0689; 0690
(2016/05/19)
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- MODIFIED THERAPEUTIC AGENTS AND COMPOSITIONS THEREOF
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Methods and compositions are provided for extending the half-life of a therapeutic agent. One half-life extending moieties may be attached to a therapeutic agent, thereby extending the half life of the therapeutic agent. The modified therapeutic agents comprising a half-life extending moieties attached to a therapeutic agent may be used to treat a disease or condition in a subject in need thereof.
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Paragraph 0319
(2016/10/04)
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- Synthesis of photoresponsive cholesterol-based azobenzene organogels: Dependence on different spacer lengths
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A series of azobenzene-cholesterol organogel compounds (M0 -M12 ) with different spacers were designed and synthesized. The molecular structures were confirmed by 1H NMR and 13C NMR spectroscopy. The rapid and reversible photoresponsive properties of the compounds were investigated by UV-vis spectroscopy. Their thermal phase behaviors were studied by DSC. The length of the spacer plays a crucial role in the gelation. Compound M6 is the only one that can gelate in ethanol, isopropanol and 1-butanol and the reversible gel-sol transitions are also investigated. To obtain visual insight into the microstructure of the gels, the typical structures of the xerogels were studied by SEM. Morphologies of the aggregates change from flower-like, network and rod with different sizes. By using IR and XRD characterization, it is found that intermolecular H-bonding, the solvents and van der Waals interaction are the main contributions to the specific superstructure.
- Ren, Yuchun,Wang, Bin,Zhang, Xiuqing
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p. 1089 - 1095
(2015/08/18)
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- A Cholesterol Containing pH-Sensitive Bistable [2]Rotaxane
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A non-symmetrical pH-sensitive bistable [2]rotaxane that bears a cholesterol unit and a tetraphenylmethane group as stopper groups was designed and synthesized in 18 steps. The successful formation of the rotaxane was proven by NMR spectroscopy and MS/MS. Besides a permanent cationic alkylated triazolium unit, the axle contains a secondary amine that can act as a second pH-sensitive binding site for a crown ether. Depending on the protonation state of this amine function, the crown ether reversibly changes its position by moving between the two binding sites along the axle, as revealed by NMR spectroscopy. A pH-sensitive bistable [2]rotaxane was synthesized and characterized by NMR spectroscopy and MS/MS. Besides an alkylated triazolium ion, the axle contains a secondary amine that acts as a second pH-sensitive binding site for a crown ether. Depending on the protonation state of this amine function, the crown ether reversibly changes its position by moving between two binding sites on the axles.
- Berg, Martin,Nozinovic, Senada,Engeser, Marianne,Lützen, Arne
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p. 5966 - 5978
(2015/09/22)
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- TARGETED DRUG DELIVERY THROUGH AFFINITY BASED LINKERS
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The current invention discloses targeted drug delivery conjugates comprising a targeting moiety linked to a drug via a molecule having an affinity for the targeting moiety. Typically, the conjugate comprises a targeting ligand and a molecule of interest, e.g., a therapeutic agent. The targeting ligand and the molecule of interest are linked to each other via an affinity ligand. The affinity ligand is further covalently or non-covalently linked to a drug or therapeutic agent. The drug can be modified to make it more soluble and so that it cleaves from the linking molecule at the target site.
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Paragraph 00253
(2015/12/08)
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- Co-liposomes comprising a lipidated multivalent RGD-peptide and a cationic gemini cholesterol induce selective gene transfection in αvβ3 and αvβ5 integrin receptor-rich cancer cells
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The αvβ3 and αvβ5 integrins, transmembrane glycoprotein receptors, are over-expressed in numerous tumors and in endothelial cells that constitute tumor blood vessels. As this protein selectively binds to the Arg-Gly-Asp (RGD) sequence containing peptides, it is an attractive way to target tumors. Herein we have developed novel formulations for integrin mediated selective gene delivery. These formulations are composed of a novel palmitoylated tetrameric RGD containing scaffold (named RAFT-RGD), cationic gemini cholesterol (GL5) and a natural helper lipid 1,2-dioleoyl-l-α- glycero-3-phosphatidylethanolamine (DOPE). We have optimized a co-liposomal formulation to introduce the multivalent RGD-containing macromolecule in GL5: DOPE (GL5D) mixture to produce GL5D-RGD. We have unambiguously shown the selectivity of these formulations towards cancer cells that over express αvβ3 and αvβ5 integrins. Two reporter plasmids, pEGFP-C3 and PGL-3, were employed for the transfection experiments and it was shown that GL5D-RGD liposomes increased exclusively the transfection in αvβ3 and αvβ5-overexpressing HeLa cells. This journal is the Partner Organisations 2014.
- Misra, Santosh K.,Kondaiah, Paturu,Bhattacharya, Santanu,Boturyn, Didier,Dumy, Pascal
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supporting information
p. 5758 - 5767
(2014/11/08)
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- Syntheses, transfection efficacy and cell toxicity properties of novel cholesterol-based gemini lipids having hydroxyethyl head group
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We have synthesized five new cholesterol based gemini cationic lipids possessing hydroxyethyl (-CH2CH2OH) function on each head group, which differ in the length of the polymethylene spacer chain. These gemini lipids are important for gene delivery processes as they possess pre-optimized molecular features, e.g., cholesterol backbone, ether linkage and a variable spacer chain between both the headgroups of the gemini lipids. Cationic liposomes were prepared from each of these lipids individually and as a mixture of individual cationic gemini lipid and 1,2-dioleoyl phosphatidylethanolamine (DOPE). Each gemini lipid based formulation induced better transfection activity than that of their monomeric counterpart. One such gemini lipid with a -(CH2)12- spacer, HG-12, showed dramatic increase in the mean fluorescence intensity due to the expression of green-fluorescence protein (GFP) in the presence of 10% FBS compared to the conditions where there was no serum. Other gemini lipids retained their gene transfection efficiency without any marked decrease in the presence of serum. The only exception was seen with the gemini with a -(CH2) 3- spacer, HG-3, which on gene transfection in the presence of 10% FBS lost ~70% of its transfection efficiency. Overall the gemini lipid with a -(CH2)5- spacer, HG-5, showed the highest transfection activity at N/P (lipid/DNA) ratio of 0.5 and lipid:DOPE molar ratio of 2. Upon comparison of the relevant parameters, e.g., %-transfected cells, the amount of DNA transfected to each cell and %-cell viability all together against Lipofectamine 2000, one of the best commercial transfecting agents, the optimized lipid formulation based on DOPE/HG-5 was found to be comparable. In terms of its ability to induce gene-transfer in the presence of serum and shelf-life DOPE/HG-5 liposome was found to be superior to its commercial counterpart. Confocal imaging analysis confirmed that in the presence of 10% serum using a Lipid:DOPE of 1:4 and N/P charge ratio of 0.75 with 1.2 μg DNA per well, HG-5 is better than Lipofectamine 2000.
- Biswas, Joydeep,Mishra, Santosh K.,Kondaiah, Paturu,Bhattacharya, Santanu
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experimental part
p. 4600 - 4613
(2011/07/09)
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- Visual chiral recognition through enantioselective metallogel collapsing: Synthesis, characterization, and application of platinum-steroid low-molecular-mass gelators
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Seeing is believing: The visual chiral recognition of (R)- and (S)-binap has been realized through an enantioselective breakdown of metallogels prepared from novel aromatic-linker-steroidal-type pincer platinum gelators. Van der Waals interactions, π stacking, and metal-metal bonding are responsible for the aggregation and chiral recognition. Copyright
- Tu, Tao,Fang, Weiwei,Bao, Xiaoling,Li, Xinbao,Doetz, Karl Heinz
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supporting information; scheme or table
p. 6601 - 6605
(2011/09/15)
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- The synthesis of cholesterol-based cationic lipids with trimethylamine head and the effect of spacer structures on transfection efficiency
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Five cholesterol-based cationic lipids were newly synthesized based on cholest-5-en-3β-oxyethane-N,N,N-trimethylammonium bromide (Chol-ETA) structure where the cholesterol backbone is linked to cationic head via various lengths of ether-linked carbon spacer. The transfection efficiency of these compounds was increased in order of three (Chol-PRO) four (Chol-BTA) two (Chol-ETA) methylene unit in their spacer, and was decreased by an addition of isomethyl group to Chol-PRO spacer. In case of the presence of multiple bonds in the spacer, it required the more cationic lipids in liposome formulation than single bond in the spacer to present similar transfection efficiency. Crown Copyright
- Kim, Bieong-Kil,Bae, Yun-Ui,Doh, Kyung-Oh,Hwang, Guen-Bae,Lee, Sung-Hye,Kang, Hyungu,Seu, Young-Bae
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scheme or table
p. 3734 - 3737
(2011/08/06)
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- Chlorin e6-cholesterol conjugate and its copper complex. Simple synthesis and entrapping in phospholipid vesicles
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Synthesis of 13′[(cholest-5-en)-3β-yloxyethoxycarbamoyl]-chlorin e6 starting from methylpheophorbide and 3β(2-hydroxy)-ethoxycholest-5-ene is presented, as well as the preparation of related copper complex. Both conjugates obtained may be simply incorporated in phosphatidyl choline vesicles.
- Nikolaeva, Irina A.,Misharin, Alexander Yu.,Ponomarev, Gelii V.,Timofeev, Vladimir P.,Tkachev, Yaroslav V.
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scheme or table
p. 2872 - 2875
(2010/07/10)
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- Design, synthesis, and in vitro gene delivery efficacies of novel cholesterol-based gemini cationic lipids and their serum compatibility: A structure-activity investigation
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Five cholesterol-based gemini cationic lipids, which differ in the length of the spacer [-(CH2)n-] chain between the head groups, have been synthesized. These lipids are useful as nonviral gene delivery agents, and all cholesterol-based gemini lipids (2a-2e) are better transfecting agents than their monomeric lipid counterpart 1. Transfection efficiency of all the gemini lipids except lipid 2a [-(CH2)3-] was maintained even when the serum was present during the transfection conditions as compared to the monomeric lipid 1, with which a dramatic decrease in transfection efficiency was observed. With the increase in spacer chain length from propanediyl [-(CH2)3-] to pentanediyl [-(CH 2)5-], transfection efficiency increased both in the absence and presence of serum. However, transfection efficiency decreased with further increase in the length from the pentanediyl [-(CH2) 5-] to the dodecanediyl [-(CH2)12-] spacer. Among these gemini lipids 2c showed the highest transfection activity, which was also greater than that of the commercially available formulation.
- Bajaj, Avinash,Kondiah, Paturu,Bhattacharya, Santanu
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p. 2432 - 2442
(2008/02/03)
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- Membrane formation from oxyethylene bearing cationic cholesterol derivatives
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Eight cholesterol based amphiphiles, 1a-d and 2a-d, bearing differing lengths of oxyethylene units at different locations, have been synthesized. Membrane formation from the aqueous suspensions of these compounds has been confirmed by transmission electron microscopy and dye entrapment. X-Ray diffraction and fluorescence anisotropy measurements reveal modulation of the membrane characteristics by both the length and location of the oxyethylene segment.
- Bhattacharya,Krishnan-Ghosh
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p. 891 - 894
(2007/10/03)
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- Microbiological degradation of sterol side chains to a 17-keto group
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The side chains of sterols are degraded by fermentation with microorganisms capable of doing so in an improved manner by employing in such fermentations sterol derivatives of the formula STR1 wherein n is 1 or 2; R1 is H or lower alkyl, R2 is alkyl, whose chain optionally is interrupted by an oxygen atom, or when n is 2, also a hydrogen atom; and R3 is a sterol side chain.
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