Structure-Activity of Three Phospholipid Analogues Towards Inhibition of Phospholipase A2 in Macrophages

Letourneux, Yves; Bourass, J.; Boucrot, P; Elkihel, L.; Petit, J

doi:10.1006/phrs.1996.0107

Cited by 4 publications

(6 citation statements)

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“…No mention of reaction yields or information on the difficulty of the SCHEME 18 Downloaded by [The University of Manchester Library] at 02: 25 12 October 2014 thiolate substitution on the tosylate was given in this paper, and experimental descriptions provided minimal detail. Presumably, the thiolate, a stronger nucleophile compared to thioacetate, can effect the substitution more readily but this was not specifically documented [86].…”

Section: Thioether Lipidsmentioning

confidence: 97%

“…The resulting octylthio derivative 60 was deprotected with ZnBr 2 -MeOH to give 61. PC installation using 2-chloro-2-oxo-1,3,2-dioxophospholane ensued (scheme 18) [86]. No mention of reaction yields or information on the difficulty of the SCHEME 18 Downloaded by [The University of Manchester Library] at 02: 25 12 October 2014 thiolate substitution on the tosylate was given in this paper, and experimental descriptions provided minimal detail.…”

Section: Thioether Lipidsmentioning

confidence: 98%

“…To study the structure-activity of phospholipid analog towards inhibition of phospholipase A 2 activity in ionophore A23187 stimulated macrophages, Letourneux et al [86] prepared racemic 1-octyl-2-octylthio-2-deoxyglycerophosphocholine (59). They found it had a higher inhibitory effect than mepacrine, dexamethasone or bromophenacyl bromide at corresponding concentrations; although, it was less effective than sn-2 ether or amide analogs.…”

Section: Thioether Lipidsmentioning

confidence: 99%

“…The hydroxy group was activated with tosyl chloride, permitting nucleophilic displacement [86]. The resulting octylthio derivative 60 was deprotected with ZnBr 2 -MeOH to give 61.…”

Section: Thioether Lipidsmentioning

confidence: 99%

“…The discovery of the trithiocarbonates was somewhat fortuitous as the authors intended to prepare 1,2-bis(methylxanthate) 85 by the reaction of potassium methylxanthate and ditosylate 86. The ditosylate (86) was secured through the reaction of 1-trityl glycerol 87 that, in turn, was prepared from D-mannitol. Reaction of 86 and in situ derived potassium methylxanthate did not provide a 1,2-bis(methylxanthate), but trithiocarbonate 88 was obtained instead.…”

Section: Sn-12-dithio Lipidsmentioning

confidence: 99%

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Synthesis of sulfur-containing glycerophospholipids

Davy

Wang

Notter

et al. 2007

Journal of Sulfur Chemistry

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Section: Thioether Lipidsmentioning

confidence: 97%

Section: Thioether Lipidsmentioning

confidence: 98%

Section: Thioether Lipidsmentioning

confidence: 99%

“…The hydroxy group was activated with tosyl chloride, permitting nucleophilic displacement [86]. The resulting octylthio derivative 60 was deprotected with ZnBr 2 -MeOH to give 61.…”

Section: Thioether Lipidsmentioning

confidence: 99%

Section: Sn-12-dithio Lipidsmentioning

confidence: 99%

See 3 more Smart Citations

Synthesis of sulfur-containing glycerophospholipids

Davy

Wang

Notter

et al. 2007

Journal of Sulfur Chemistry

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Synthesis and interfacial behavior of sulfur-containing analogs of lung surfactant dipalmitoyl phosphatidylcholine

Chang

Wang

Notter

et al. 2004

Bioorganic & Medicinal Chemistry Letters

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Secreted and intracellular phospholipases A₂ inhibition by 1‐decyl 2‐octyl‐glycerophosphocholine in rat peritoneal macrophages

Boucrot¹,

Bobin‐Dubigeon

Elkihel

et al. 1998

Fundamemntal Clinical Pharma

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Compounds able to inhibit phospholipases A2 can be considered as potential anti-inflammatory drugs. In this respect, the inhibitory effect of the phospholipid analogue 1-decyl 2-octyl-rac-glycero-3-phosphocholine (decyloctyl-GPC) added to the culture medium of rat peritoneal macrophages stimulated with ionophore A23187 was determined. (a) The substrate of phospholipase A2 1-octadecanoyl 2-[14C]eicosatetraenoyl-sn-glycero-3-phosphocholine ([14C]20:4-GPC) was added to the culture medium. In macrophages + extracellular fluids, its hydrolysis at the 2-position, produced [14C]non-phosphorous lipids which reached 12% of the dose at 0.14 microM, 73% at 0.9 and > 90% at 1.6 microM; in experiments where macrophages and extracellular fluids were analyzed separately, decyloctyl-GPC initially added at 4 microM, significantly inhibited the release of [14C]fatty acids and the eicosanoid synthesis, demonstrating its ability to inhibit secreted and/or intracellular phospholipases A2. (b) Extracellular fluids were separated from the macrophages and incubated with [14C]20:4-GPC: 48% of the dose was hydrolyzed by extracellular fluid-associated secreted phospholipase A2 and decyloctyl-GPC at 3 microM, reduced this hydrolysis by 50%. (c) [3H]arachidonic acid ([3H]20:4) was added to the culture medium and was esterified in the macrophage membrane phospholipids. Activation of intracellular phospholipase A2 induced the release of [3H] fatty acids and eicosanoid synthesis. These releases were inhibited by 50% with decyloctyl-GPC added at 4 microM. (d) [3H]20:4 and [14C]20:4-GPC were added to the culture medium of the macrophages. [3H] and [14C] fatty acids and eicosanoids were released in macrophages or extracellular fluids. They were significantly reduced by the phospholipid analogue added at 4 microM. It is concluded that secreted and intracellular phospholipases A2 were both inhibited by decyloctyl-GPC which extensively reduced the 20:4 release from exogenous and membrane phospholipids and therefore eicosanoid synthesis.

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Structure-Activity of Three Phospholipid Analogues Towards Inhibition of Phospholipase A2 in Macrophages

Cited by 4 publications

References 0 publications

Synthesis of sulfur-containing glycerophospholipids

Synthesis of sulfur-containing glycerophospholipids

Synthesis and interfacial behavior of sulfur-containing analogs of lung surfactant dipalmitoyl phosphatidylcholine

Secreted and intracellular phospholipases A₂ inhibition by 1‐decyl 2‐octyl‐glycerophosphocholine in rat peritoneal macrophages

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Structure-Activity of Three Phospholipid Analogues Towards Inhibition of Phospholipase A2 in Macrophages

Cited by 4 publications

References 0 publications

Synthesis of sulfur-containing glycerophospholipids

Synthesis of sulfur-containing glycerophospholipids

Synthesis and interfacial behavior of sulfur-containing analogs of lung surfactant dipalmitoyl phosphatidylcholine

Secreted and intracellular phospholipases A2 inhibition by 1‐decyl 2‐octyl‐glycerophosphocholine in rat peritoneal macrophages

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Product

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Secreted and intracellular phospholipases A₂ inhibition by 1‐decyl 2‐octyl‐glycerophosphocholine in rat peritoneal macrophages