Analogs of alkyllysophospholipids: Chemistry, effects on the molecular level and their consequences for normal and malignant cells

Brachwitz, H.; Vollgraf, Christine

doi:10.1016/0163-7258(95)00001-w

Cited by 94 publications

(51 citation statements)

References 199 publications

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“…It has been demonstrated that ether lysophospholipids stimulate the oxidative burst of peritoneal macrophages (Brachwitz & Vollgraf 1995) and boost glucose consumption in these cells (Hartung 1983). In activated tumour macrophages, increases result in the production of reactiveoxygen metabolites, such as H 2 O 2 and superoxide O 2 (Hayashi et al 1985).…”

Section: Discussionmentioning

confidence: 99%

Leishmanicidal Activity of Edelfosine, Miltefosine and Ilmofosine

Azzouz¹,

Maache²,

Garcia³

et al. 2005

Basic Clin Pharma Tox

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Abstract:The anti-proliferative action of three alkyl-lysophospholipid derivatives, edelfosine (ET-OCH), miltefosine (Hexadecylphosphocholine), and ilmofosine (BM 14.440) has been studied on the promastigotes and amastigotes of Leishmania donovani. The effect of the three drugs has previously been studied, but the action mode was not clearly elucidated. In this study the effect on the intracellular amastigote forms was evaluated by two different methods: the traditional method, counting the amastigotes within the macrophages stained with Giemsa; and by a new method, staining the nuclear macrophages and amastigotes with ethidium bromide and counting the different population by flow cytometry. This new method, based on the flow cytometry, shows an advantage for evaluating the anti-proliferative effects in intracellular parasites. The ED50 were calculated for the drug activity after 72 hr, and for the three alkyl-lysophospholipid derivatives it were in the range of 26.73-33.31 mM against promastigotes and in the range of 16.46-23.16 against amastigotes. Also, studying the effect against macrophages J774A1, the ED50 were in the range of 24.28-26.38 mM. The effect of the alkyl-lysophospholipids in the macromolecular biosynthesis of the Leishmania donovani, was studied comparing the incorporation of labelled analogues ([

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Section: Discussionmentioning

confidence: 99%

Leishmanicidal Activity of Edelfosine, Miltefosine and Ilmofosine

Azzouz¹,

Maache²,

Garcia³

et al. 2005

Basic Clin Pharma Tox

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“…Miltefosine (hexadecylphosphocholine) is one of several alkyllysophospholipid derivatives collectively known as alkylphosphocholines that were originally developed as anticancer agents (6). The biocidal action of miltefosine against Leishmania species was demonstrated in the mid 1980s (3,7).…”

mentioning

confidence: 99%

In Vitro Bactericidal Activity of the Antiprotozoal Drug Miltefosine against Streptococcus pneumoniae and Other Pathogenic Streptococci

Llull

Rivas

Garcı́a³

2007

Antimicrob Agents Chemother

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“…Synthetic alkyl ether phospholipids represent a promising class of antitum or agents that, unlike most conventional chemotherapeutic drugs, do not target the DNA but act at the level of the cell membrane [1][2][3][4]. The prototype of these antineoplastic ether phospholipids is ET-18-OCH 3 (edelfosine, 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) [1][2][3][4] that exerts a selective cytotoxic action against cancer cells [1,5].…”

Section: Introductionmentioning

confidence: 99%

“…The prototype of these antineoplastic ether phospholipids is ET-18-OCH 3 (edelfosine, 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) [1][2][3][4] that exerts a selective cytotoxic action against cancer cells [1,5]. The antitumor effect of edelfosine is based mainly on two different mechanisms that can act synergistically against neoplastic growth.…”

Section: Introductionmentioning

confidence: 99%

Quantitative determination of the antitumor alkyl ether phospholipid edelfosine by reversed-phase liquid chromatography–electrospray mass spectrometry: application to cell uptake studies and characterization of drug delivery systems

Blanco-Prieto

Campanero

Mollinedo

2004

Journal of Chromatography B

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Edelfosine is a synthetic alkyl ether phospholipid that represents a promising class of antitumor agents. However, analytical methods to measure these type compounds are scarce. The lack of a reliable methodology to quantify edelfosine is a major problem in ongoing and scheduled preclinical and clinical trials with this drug. We evaluated the applicability of high-performance liquid chromatography-mass spectrometry to determine edelfosine in biological samples and polymeric delivery systems. Sample pre-treatment involved polymer precipitation or cell lysis with methanol. HPLC separation was performed on an Alltima RP18 narrow-bore column and edelfosine quantification was done by electrospray ionization mass spectrometry (ESI-MS) using positive ion mode and selected ion monitoring. Assays were linear in the tested range of 0.3-10 µg/ml. The limit of quantification was 0.3 ng/sample in both matrices, namely biological samples and polymeric delivery systems. The interassay precision ranging from 0.79 to 1.49%, with relative errors of -6.7% and 12.8%. Mean extraction recovery was 95.6%.HPLC-ESI-MS is a reliable system for edelfosine analysis and quantification in samples from different sources, combining advantages of full automation (rapidity, ease of use, no need of extensive extraction procedures) with high analytical performance and throughput.

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Analogs of alkyllysophospholipids: Chemistry, effects on the molecular level and their consequences for normal and malignant cells

Cited by 94 publications

References 199 publications

Leishmanicidal Activity of Edelfosine, Miltefosine and Ilmofosine

Leishmanicidal Activity of Edelfosine, Miltefosine and Ilmofosine

In Vitro Bactericidal Activity of the Antiprotozoal Drug Miltefosine against Streptococcus pneumoniae and Other Pathogenic Streptococci

Quantitative determination of the antitumor alkyl ether phospholipid edelfosine by reversed-phase liquid chromatography–electrospray mass spectrometry: application to cell uptake studies and characterization of drug delivery systems

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