- Design, synthesis and cytotoxicity of chimeric erlotinib-alkylphospholipid hybrids
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Two series of erlotinib-alkylphospholipid hybrids were prepared and evaluated for their antiproliferative activities against a panel of four cell lines representing lung, breast, liver and skin cancers using erlotinib and miltefosine as reference standards. Amide analogs elicited more enhanced cytotoxic activity than analogous esters. Amide derivatives 8d and 8e exhibited promising broad-spectrum antiproliferative activity and higher efficacy than reference erlotinib and miltefosine. Their cellular GI50 values was in the ranges of 24.7–46.9 μM and 26.8–43.1 μM for 8e and 8d respectively. Assay results of the inhibitory activity of the prepared compounds on EGFR kinase reaction and Akt phosphorylation in conjugation with statistical correlation analysis indicated that other mechanisms might contribute to their elicited cytotoxicities. In addition, statistical correlation analysis revealed that mechanisms of elicited cytotoxicities for amide series might be different from ester series. In addition, correlation analysis indicated variations in the mechanisms according to the types of cell line.
- Alam, Md. Maqusood,Hassan, Ahmed H.E.,Lee, Kun Won,Cho, Min Chang,Yang, Ji Seul,Song, Jiho,Min, Kyung Hoon,Hong, Jongki,Kim, Dong-Hyun,Lee, Yong Sup
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supporting information
p. 51 - 62
(2018/11/27)
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- Synthesis of natural 1- O -alkylglycerols: A study on the chemoselective opening of the epoxide ring by onium quaternary salts (N and P) and ionic liquids
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A chemoselective route for the synthesis of 1-O-alkylglycerols chimyl (1), batyl (2), and selachyl (3) is reported. These compounds can be naturally isolated from shark liver oil and the skin of animals such as stingrays and chimeras and exhibit potential anti-fouling activity. The synthetic approach developed in this work included two distinct methods of preparation. The first was based on solvent-free reactions catalyzed by onium quaternary salts (N and P) and ionic liquids; the second methodology was based on a series of one-pot reactions.
- Nascimento, Thiana Santiago,Braga, Esther Faria,Casaes Gomes, Giselle Cristina,Batista, William Rom?o,Mazzei Albert, André Luís,Capella Lopes, Rosangela Sabbatini,Lopes, Claudio Cerqueira
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p. 1050 - 1054
(2020/01/23)
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- Synthesis of alkyl-glycerolipids standards for gas chromatography analysis: Application for chimera and shark liver oils
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Natural O-alkyl-glycerolipids, also known as alkyl-ether-lipids (AEL), feature a long fatty alkyl chain linked to the glycerol unit by an ether bond. AEL are ubiquitously found in different tissues but, are abundant in shark liver oil, breast milk, red blood cells, blood plasma, and bone marrow. Only a few AEL are commercially available, while many others with saturated or mono-unsaturated alkyl chains of variable length are not available. These compounds are, however, necessary as standards for analytical methods. Here, we investigated different reported procedures and we adapted some of them to prepare a series of 1-O-alkyl-glycerols featuring mainly saturated alkyl chains of various lengths (14:0, 16:0, 17:0, 19:0, 20:0, 22:0) and two monounsaturated chains (16:1, 18:1). All of these standards were fully characterized by NMR and GC-MS. Finally, we used these standards to identify the AEL subtypes in shark and chimera liver oils. The distribution of the identified AEL were: 14:0 (20–24%), 16:0 (42–54%) and 18:1 (6–16%) and, to a lesser extent, (0.2–2%) for each of the following: 16:1, 17:0, 18:0, and 20:0. These standards open the possibilities to identify AEL subtypes in tumours and compare their composition to those of non-tumour tissues.
- Pinault, Michelle,Guimaraes, Cyrille,Couthon, Hélène,Thibonnet, Jér?me,Fontaine, Delphine,Chant?me, Aurélie,Chevalier, Stephan,Besson, Pierre,Jaffrès, Paul-Alain,Vandier, Christophe
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- PROCESS FOR PREPARING A POLYOL ETHER
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The present invention relates to a process for preparing a polyol ether of formula (I), comprising a step of reductive alkylation involving a compound of general formula (II) and a compound of general formula (III): in which R1, R2, R3 and R4 are as defined in claim 1.
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Paragraph 0130
(2014/02/16)
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- 1-O-Alkyl (di)glycerol ethers synthesis from methyl esters and triglycerides by two pathways: Catalytic reductive alkylation and transesterification/reduction
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From available and bio-sourced methyl esters, monoglycerides or oleic sunflower refined oil, the corresponding 1-O-alkyl (di)glycerol ethers were obtained in both high yields and selectivity by two different pathways. With methyl esters, a reductive alkylation with (di)glycerol was realized under 50 bar hydrogen pressure in the presence of 1 mol% of Pd/C and an acid co-catalyst. A second two step procedure was evaluated from methyl esters or triolein and consisted of a first transesterification to the corresponding monoglyceride with a BaO/Al2O3 catalyst, then its reduction to the desired glycerol monoether with a recyclable heterogeneous catalytic system Pd/C and Amberlyst 35 under H2 pressure. In addition, a mechanism for the reaction was also proposed.
- Sutter, Marc,Dayoub, Wissam,Metay, Estelle,Raoul, Yann,Lemaire, Marc
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supporting information
p. 786 - 797
(2013/04/24)
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- Selective synthesis of 1-O-Alkyl(poly)glycerol ethers by catalytic reductive alkylation of carboxylic acids with a recyclable catalytic system
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(Poly)glycerol monoethers were synthesized in good yield and selectivity by the catalytic reductive alkylation of glycerol, diglycerol, and triglycerol with readily available, cheap and/or bio-sourced carboxylic acids. The reaction was catalyzed by 1 mol % of Pd/C under 50 bar H2 using an acid ion-exchange resin as a recyclable cocatalyst. The catalytic system was recycled several times, and a mechanism is proposed for this transformation.
- Sutter, Marc,Dayoub, Wissam,Metay, Estelle,Raoul, Yann,Lemaire, Marc
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p. 2397 - 2409
(2013/02/23)
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- In vitro intestinal bioaccessibility of alkylglycerols versus triacylglycerols as vehicles of butyric acid
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Butyric acid has been the subject of much attention last years due to its bioactivity. However, the potential advantages of butyrate are limited by the problem to reach enough plasma concentrations; therefore, pro-drugs have been proposed as an alternative to natural butyrate. A comparative study on in vitro intestinal digestion of 2,3-dibutyroil-1-O-octadecyl glycerol (D-SCAKG) and tributyrin (TB), as potential pro-drugs of butyric acid, was performed. Aliquots were taken at different times of digestion for studying the extent and rate of hydrolysis of both substrates. The micellar phase (MP) and oily phase (OP) formed in the digestion media were separated and their composition in lipid products was analyzed. Initially, it was confirmed that the in vitro model reproduced physiological results by testing against olive oil as a standard lipid. The progress of in vitro intestinal digestion of D-SCAKG was slower than that of TB. TB hydrolyzed completely to butyric acid, whereas D-SCAKG mainly yielded 2-butyroil-1-O-octadecyl glycerol (M-SCAKG), followed by butyric acid and 1-O-octadecyl glycerol (AKG). The MP from both substrates mainly consisted of butyric acid. Minor levels of M-SCAKG and AKG were also found in the MP after hydrolysis of D-SCAKG, the M-SCAKG being mainly distributed in the OP. Therefore, D-SCAKG produced a stable form of esterified butyric acid as M-SCAKG after in vitro intestinal digestion, unlike TB. Additionally, such a product would integrate both bioactive compounds, butyric acid and alkylglycerol, within the same molecule. Free butyric acid and AKG would be also released, which are lipid products of interest as well. AOCS 2011.
- Martin, Diana,Moran-Valero, Maria I.,Senorans, Francisco J.,Reglero, Guillermo,Torres, Carlos F.
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experimental part
p. 277 - 285
(2012/01/17)
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- Lipase-catalysed kinetic resolution of 1-O-alkylglycerols by sequential transesterification
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The natural S-configured chimyl, batyl and selachyl alcohols of the 1-O-alkylglycerol type were prepared by enantioselective lipase-catalysed transesterification. Their racemates were synthesised in two steps by reacting racemic solketal with the bromides of the corresponding fatty alcohols and a subsequent conversion of the intermediates into the 1-O-alkylglycerols by deprotection under acidic aqueous conditions. The Pseudomonas fluorescens lipase was employed to kinetically resolve the racemic 1-O-alkylglycerols by a sequential diacetylation process to afford them virtually enantiomerically pure. Dramatic enantioselectivity increase was observed for the saturated chimyl (E = 17-32) and batyl (E = 14-38) alcohols at decreased temperature, whereas for the monounsaturated selachyl (E = 12-13) alcohol no such temperature effects were observed.
- Halldorsson, Arnar,Thordarson, Pall,Kristinsson, Bjorn,Magnusson, Carlos D.,Haraldsson, Gudmundur G.
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p. 2893 - 2899
(2007/10/03)
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- Kinetic resolution of 1-O-alkylglycerols by lipase
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Pseudomonas sp. lipase was employed to resolve kinetically 1-O- alkylglycerols by a sequential diacylation process. Only low or moderate E- values were obtained, but at approximately 60% conversion enantiomerically pure monoacetates were obtained of the natural S-configuration for glyceryl ether lipids.
- Haraldsson, Gudmundur G.,Thordarson, Pall,Halldorsson, Arnar,Kristinsson, Bjorn
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p. 3671 - 3674
(2007/10/03)
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- Bioactive compounds from a new species of Sinularia soft coral
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Compounds 1-3.5 and 6, which showed antibacterial activities, have been isolated from a new species of Sinularia soft coral.
- Subrahmanyam,Kulatheeswaran
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p. 1388 - 1390
(2007/10/03)
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- Phospholipase-A2-mediated stereoselective synthesis of (R)-1-O-alkylglycero-3-phosphate and alkyl-acyl analogues: Application for synthesis of radiolabelled biosynthetic precursors of cell surface glycoconjugates of Leishmania donovani
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Stereoselective syntheses of (R)-1-O-alkylglycero-3-phosphate and alkyl-acyl analogues have been achieved using glycerol as starting material by an efficient application of Phospholipase-A2 enzyme from Naja mocambique mocambique. This synthetic strategy allows a high yielding preparation of radiolabelled [14C] and chirally pure biosynthetic precursors of GIPLs and LPG cell surface molecules of promastigote and amastigote forms of the protozoan parasite Leishmania donovani.
- Sahai, Parmeshwari,Vishwakarma, Ram A.
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p. 1845 - 1849
(2007/10/03)
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- Disubstituted tetrahydrofurans and dioxolanes as PAF antagonists
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A new series of disubstituted tetrahydrofuran and dioxolane derivatives were prepared and evaluated for their PAF antagonist activity in the PAF-induced in vitro platelet-aggregation and in vivo hypotension tests. Several of these compounds exhibited more potent activity than the structurally related 2-[N-acetyl-N-[[[[2-methoxy-3-[(octadecylcarbamoyl)oxy]propoxy] carbonyl]amino]methyl]-1-ethylpyridinium chloride (CV-6209, 3) in the in vitro assay, whereas all showed less potency in the in vivo test. The role of both the substituent nature and the placement and number of oxygen atoms in the ring are discussed. A qualitative SAR study was carried out on these nuclei.
- Bartroli,Carceller,Merlos,Garcia-Rafanell,Forn
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p. 373 - 386
(2007/10/02)
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- Synthesis of 1-O-alkyl-2-O-acetyl-Sn-3-glyceryl-3-phosphoryl choline the enantiomer of platelet activating factor (PAF)
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A novel sterospecific synthesis of biologically active ether-phospholipids (PAF) is reported, involving chemoenzymatic approach.
- Kumar,Shanker
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p. 1763 - 1768
(2007/10/02)
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- Synthesis of 1-O-alkyl-2-O-methyl-glycerophospholipids with potential antitumor activity
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Some synthetic alkyl-lysophospholipid analogs have been described as a new class of immunopotentiating and antitumor agents. Among them, 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine has been reported to possess the highest antitumor activity. A new method for the synthesis of this compound and of the ethanolamine- and serine-containing analog is reported. 1-Alkyl-2-methyl-rac-glycerol, prepared from 1,2-isopropylidene-glycerol, is phosphorylated and the intermediate is condensed either with N-t-BOC-protected ethanolamine or with N-t-BOC-protected serine benzhydryl ester. The choline-derivative is obtained by methylation with CH3I of the ethanolamine derivative. The same synthetic sequence has been used also for synthesizing compounds unsaturated at the fatty alkyl chain in position 1 of the glycerol moiety. Preliminary observation are reported on the selective cytolytic action of the compounds on a tumor cell line.
- Alunni-Bistocchi,Orvietani,Ricci,Binaglia,Orlando,Orlando
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p. 499 - 509
(2007/10/02)
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