Structure-activity relationships in platelet-activating factor (PAF). 7. Tetrahydrofuran derivatives as dual PAF antagonists and acetylcholinesterase inhibitors. Synthesis and PAF-antagonistic activity

Texier, Laurence Le; Favre, Edith; Redeuilh, Catherine; Blavet, N.; Bellahsene, Tounes; Dive, Georges; Pirotzky, E.; Godfroid, Jean‐Jacques

doi:10.1016/0929-7855(95)00046-1

Cited by 13 publications

(9 citation statements)

References 18 publications

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“…When produced, stimulated macrophages were able to transmigrate across the blood-brain barrier, participate in a variety of neurodestructive events and may play a pivotal role in neurodegenerative conditions [2,14,50]. Therefore, the effects of PMS777, a new acetylcholinesterase inhibitor with anti-PAF activity [24,25], were investigated on a macrophage cell line by measuring oxidative stress/inflammation markers in comparison with tacrine, first marketed AChE inhibitor against AD, also known to reduce oxidative injury in rat pheochromocytoma cells [30].…”

Section: Discussionmentioning

confidence: 99%

“…The tetrahydrofuran derivative, PMS777 (nomenclature Unité de Pharmacochimie Moléculaire et Systèmes Membranaires, Université Paris7) was previously synthesized as described [24]. Fluorescent probes were ordered from Molecular Probes (Leiden, The Netherlands).…”

Section: Reagentsmentioning

confidence: 99%

“…Searching for neuroprotective agents, and taking account of both the cholinergic deficiency in AD and the protective effects of PAF antagonists, it was hypothesized that an acetylcholinesterase inhibitor with anti-PAF activity could be of interest in AD. One of them, PMS777 (a tetrahydrofuran derivative), non-lethal in mice and able to reverse scopolamine-induced amnesia [24,25], was previously shown to inhibit AChE activity and platelet aggregation [24,25]. Recently, we have shown that PMS777, which improves water learning in mice, was able to prevent mnesic deficit in mice [26] and to fight oxidative injury in human neuroblastoma SK-N-SH cells [27] without cytoxic profile on cell viability, mitochondrial activity and oxidative stress in contrast with tacrine in HepG2 cells [28].…”

Section: Introductionmentioning

confidence: 99%

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A new acetylcholinesterase inhibitor with anti-PAF activity modulates oxidative stress and pro-inflammatory mediators release in stimulated RAW 264.7 macrophage cells. Comparison with tacrine

Ezoulin

Liu

Dutertre-Catella

et al. 2007

International Immunopharmacology

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Section: Discussionmentioning

confidence: 99%

Section: Reagentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A new acetylcholinesterase inhibitor with anti-PAF activity modulates oxidative stress and pro-inflammatory mediators release in stimulated RAW 264.7 macrophage cells. Comparison with tacrine

Ezoulin

Liu

Dutertre-Catella

et al. 2007

International Immunopharmacology

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“…Antibodies and Reagents PMS777 was synthesized as previously described [11]. Mouse anti-Alzheimer precursor protein monoclonal antibodies (22C11 and 6E10) were obtained from Chemicon International Inc. (Temecula, CA).…”

Section: Methodsmentioning

confidence: 99%

“…PMS777 (Fig. 1) is one of a family of new cholinesterase inhibitors synthesized by Le Texier et al that also has anti-platelet activated factor (PAF) activity [11,12]. Previous studies have indicated that PMS777 inhibited acetylcholinesterase activity with IC50 at 0.8 lM and antagonized PAF activity with IC50 at 8 lM [11,12].…”

Section: Introductionmentioning

confidence: 99%

PMS777, a New Cholinesterase Inhibitor with Anti-Platelet Activated Factor Activity, Regulates Amyloid Precursor Protein Processing In Vitro

et al. 2008

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Alzheimer's disease (AD) is a neurodegenerative disorder characterized clinically by progressive impairment of memory and cognition. Previous data have shown that beta-amyloid (Abeta) cascade plays a central role in AD pathophysiology and thus drugs regulate amyloid precursor protein (APP) metabolism may have therapeutic potential. Here the effects of PMS777, a new cholinesterase inhibitor with anti-platelet activated factor activity, on APP processing were investigated. Using SH-SY5Y(APP695) cells, it showed that PMS777 treatment caused significant decreased secretion of sAPPalpha into the conditioned media without affecting cellular holoAPP synthesis. When PC12 cells were incubated with PMS777, the same effect was observed. The data also indicated that 10 muM PMS777 incubation decreased the release of Abeta42 into the cell media as compared with vehicle group in SH-SY5Y(APP695) cells. Pretreatment of cells with M-receptor scopolamine antagonized the decreased secretion of sAPPalpha induced by PMS777, but N-receptor alpha-bungarotoxin pretreatment did not have such an effect. These results indicated that PMS777 could modulate APP processing in vitro and that decreasing Abeta generation might demonstrate its therapeutic potential in AD.

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Study of inclusion complexes of acridine with β‐ and (2,6‐di‐O‐methyl)‐β‐cyclodextrin by use of solubility diagrams and NMR spectroscopy

Correia

Bezzenine

Ronzani

et al. 2002

J of Physical Organic Chem

101

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Previous molecular modeling studies, in our laboratory, have shown that some esters of type RCOO(CH2) nC5H5N+Cl− are potentially active against Alzheimer's disease. We have also demonstrated that acridine, which has strong anticholinesterase activity appears to be a suitable R substituent. The main obstacle to the possible pharmaceutical application of these compounds is their limited solubility in water, which is due to the poor aqueous solubility of acridine itself (0.26 mM). Inclusion complexation with cyclodextrins may overcome this problem. Solubility diagrams and NMR spectroscopy were used to study the inclusion of acridine (Acr) within β‐cyclodextrin (βCD) and heptakis(2,6‐di‐O‐methyl)cyclomaltoheptose (DMβCD). A 1:1 complex was formed for the Acr–βCD system and both 1:1 and 2:1 complexes for the Acr–DMβCD system (apparent Ka 215 ± 20 and 1150 ± 100 M −1, respectively). Data from 1H NMR studies corrected the assignment of the acridine H1, H8 and H4, H5 protons in D2O, which have been erroneously assigned in previous publications. 1H spin–lattice relaxation times T1 measured with selective, non‐selective and null inversion characterize the dynamics of the inclusion complexes. Geometric features of the host–guest inclusion complexes were inferred from intermolecular dipolar interactions obtained by 2D adiabatic off‐resonance ROESY experiments. A more detailed picture of the structure of the inclusion complexes was obtained by combining NMR structural data and molecular modeling (docking, dynamics under NMR constraints and energy calculations). Copyright © 2002 John Wiley & Sons, Ltd.

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Structure-activity relationships in platelet-activating factor (PAF). 7. Tetrahydrofuran derivatives as dual PAF antagonists and acetylcholinesterase inhibitors. Synthesis and PAF-antagonistic activity

Cited by 13 publications

References 18 publications

A new acetylcholinesterase inhibitor with anti-PAF activity modulates oxidative stress and pro-inflammatory mediators release in stimulated RAW 264.7 macrophage cells. Comparison with tacrine

A new acetylcholinesterase inhibitor with anti-PAF activity modulates oxidative stress and pro-inflammatory mediators release in stimulated RAW 264.7 macrophage cells. Comparison with tacrine

PMS777, a New Cholinesterase Inhibitor with Anti-Platelet Activated Factor Activity, Regulates Amyloid Precursor Protein Processing In Vitro

Study of inclusion complexes of acridine with β‐ and (2,6‐di‐O‐methyl)‐β‐cyclodextrin by use of solubility diagrams and NMR spectroscopy

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