- Surface modification with cholesteryl acetyl carnitine, a novel cationic agent, elevates cancer cell uptake of the PEGylated liposomes
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The present study aimed to synthesize cholesteryl acetyl carnitine (CAC), and surface modify the PEGylated liposomes with the intention of enhanced cancer cell uptake. For this, CAC synthesis was performed in amine-free esterification conditions and then four liposomal formulations of unmodified, CAC/PEG, and CAC + PEG-modified were prepared by ethanol injection method. Cytotoxicity of the liposomes was investigated in A549 cells, followed by cellular uptake assessments of coumarin 6 (C6)-loaded liposomes. The results of ATR-FTIR, 1HNMR, and 13CNMR demonstrated successful formation of CAC. A molecular docking study showed efficient binding affinities rather than carnitine to the active site of four carnitine transporters. Liposomal formulations possessed spherical morphology with a mean particle size range of 112–138 nm, narrow size distribution, and negative surface charge. All formulations had low cytotoxicity at 0.5 mg/ml, but high cytotoxicity at around 2.5 mg/ml. The lowest IC50 was obtained for CAC modified liposomes. CAC + PEG-modified liposomes had the highest cellular uptake. In conclusion, CAC + PEG modification of liposomes is an effective approach for increasing A549 cellular uptake, with low cytotoxicity at commonly applied liposome concentrations. The elevated uptake may be due to the involvement of the organic cation transporter, cationic structure, and the metabolic preference of CAC in cancer cells.
- Baradaran, Behzad,Mahmoudian, Mohammad,Sarfraz, Muhammad,Shahbazi Mojarrad, Javid,Valizadeh, Hadi,Zahednezhad, Fahimeh,Zakeri-Milani, Parvin
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- Preparation method of acetyl-L-carnitine nitrate
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The invention discloses a preparation method of acetyl-L-carnitine nitrate, which belongs to an acyclic compound with a carbon skeleton substituted by oxygen atoms, and particularly comprises preparation of acetyl-L-carnitine and preparation of acetyl-L-carnitine nitrate. According to the technical scheme, the method is simple, easy to implement, low in cost and beneficial to large-scale industrial production. According to the technical scheme provided by the invention, no catalyst is used during reaction, so that purification is facilitated; the reaction time is short and the production efficiency is high; after the reaction is finished, acetic acid is evaporated under reduced pressure, acetone is added for crystallization, acetic acid can be recycled, acetone can also be recycled in a distillation mode, solvent waste is greatly reduced, and cost is saved; and the obtained product is qualified in quality and relatively high in yield.
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Paragraph 0021; 0023
(2020/06/09)
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- Synthesis method of acetyl-L-carnitine inner salt
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The invention provides a method for synthesizing acetyl-L-carnitine simply.The method is characterized in that L-carnitine serving as a starting raw material and acetyl chloride serving as an acrylation reagent are subjected to an esterification reaction to obtain acetyl-L-carnitine hydrochloride, organic alkali is directly used for neutralizing to obtain acetyl-L-carnitine without separation, and high-quality acetyl-L-carnitine is obtained after recrystallization.According to the reaction related to the method, operation is simple, the condition is mild, aftertreatment is simple, the yield is high, and the method is a preparing way suitable for industrialization.
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Paragraph 0008; 0010
(2016/12/12)
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- Water-soluble cationic derivatives of indirubin, the active anticancer component from indigo naturalis
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To overcome the problem of poor aqueous solubility and bioavailability of indirubin-3-oximes, the compounds were modified by attaching a quaternary ammonium group at the oxime moiety. Exploring the prodrug concept, an oxime ester with acetyl-l-carnitine was prepared, and the rate of its hydrolysis was investigated to assess its suitability for clinical administration. In addition, the cytotoxic potency of new stable oxime ethers with a choline moiety and their influence on the cell cycle were tested in human cancer cell lines.
- Ginzinger, Werner,Egger, Alexander,Muehlgassner, Gerhard,Arion, Vladimir B.,Jakupec, Michael A.,Galanski, Markus,Berger, Walter,Keppler, Bernhard K.
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p. 2175 - 2185
(2013/01/15)
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- ACETYL-L-CARNITINE MALATE, PROCESS FOR PREPARING THE SAME, AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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The present invention relates to acetyl-L-carnitine malate, a process for preparing the same, and a pharmaceutical composition comprising the same. The acetyl-L-carnitine malate of the present invention has good stability, solubility, and non-hygroscopicity to be effectively used for preparing a pharmaceutical composition.
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Page/Page column 7
(2011/12/14)
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- The importance of the amide bond nearest the thiol group in enzymatic reactions of coenzyme A
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Analogues of coenzyme A (CoA) and of CoA thioesters have been prepared in which the amide bond nearest the thiol group has been modified. An analogue of acetyl-CoA in which this amide bond is replaced with an ester linkage was a good substrate for the enzymes carnitine acetyltransferase, chloramphenicol acetyltransferase, and citrate synthase, with Km values 2- to 8-fold higher than those of acetyl-CoA and Vmax values from 14 to >80% those of the natural substrate. An analogue in which an extra methylene group was inserted between the amide bond and the thiol group showed less than 4-fold diminished binding to the three enzymes but exhibited less than 1% activity relative to acetyl-CoA with carnitine acetyltransferase and no measurable activity with the other two enzymes. Analogues of several CoA thioesters in which the amide bond was replaced with a hemithioacetal linkage exhibited no measurable activity with the appropriate enzymes. The results indicate that some aspects of the amide bond and proper distance between this amide and the thiol/thioester moiety are critical for activity of CoA ester-utilizing enzymes.
- Xun, Jin,Huang, Haidong,Vogel, Kurt W.,Drueckhammer, Dale G.
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- The β-Lactone Route to a Totally Stereoselective Synthesis of Carnitine Derivatives
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The syntheses of the enantiomerically pure, carnitine-related β-lactones 10 and 12 starting from various carnitine precursors of opposite configuration (or carnitine itself) are described. (R)-3-Chlorocarnitine (20) has also been directly prepared from (S)-carnitine (14) and has been cyclized to 12 by a second inversion of configuration of the stereogenic centre.By nucleophilic attack at the carbonyl carbon, the β-lactone carnitine derivatives have been converted into esters, amides, and guanidino congeners.Following this route, it is possible to obtain the biologically active isomer (R)-carnitine (1) starting from the otherwise useless industrial by-product (S)-carnitine (14).Nucleophilic attack by selected ambident nucleophiles at the β-carbon of the same β-lactone derivatives results in a second inversion of configuration of the stereogenic centre.Besides aminocarnitine (3), chiral acetylcarnitine (2) and acetylthiocarnitine (5) have been synthesized in homochiral forms following this latter procedure. - Keywords: asymmetric ring-opening; carnitine; cyclizations; β-lactones; nucleophilic substitutions
- Bernabei, Ida,Castagnani, Roberto,Angelis, Francesco De,Fusco, Enrico De,Gianessi, Fabio,et al.
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p. 826 - 831
(2007/10/03)
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