A Phospholipid Derivative of Cytosine Arabinoside and Its Conversion to Phosphatidylinositol by Animal Tissue

Raetz, Christian R. H.; Chu, Ming; Srivastava, S.P.; Turcotte, Joseph G.

doi:10.1126/science.191910

Cited by 55 publications

(17 citation statements)

References 25 publications

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“…1) and placed in the reaction mixture (0.9 ml total volume). The assay is that of Rao and Strickland (13,14) except that (3.7 Ci/mol) and 1.0mM CDPdiglyceride (egg) were used. The reaction was stopped after 90 min with 20% trichloroacetic acid (as in Fig.…”

Section: Resultsmentioning

confidence: 99%

Replica plating and in situ enzymatic assay of animal cell colonies established on filter paper.

Raetz¹

1978

Proc. Natl. Acad. Sci. U.S.A.

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Section: Resultsmentioning

confidence: 99%

Replica plating and in situ enzymatic assay of animal cell colonies established on filter paper.

Raetz¹

1978

Proc. Natl. Acad. Sci. U.S.A.

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“…In the late 1970s and early 1980s, groups began to investigate cytotoxicity after either alkyl chain additions to ara-C or conjugation of ara-C to phospholipids [59,60]. Raetz et al used natural or synthetic phospholipids to chemically modify ara-C.…”

Section: Phospholipid Ara-c Conjugatesmentioning

confidence: 99%

“…Previous investigators have had many successes with phospholipid/nucleoside analog conjugates; however, there are still improvements that can be made to these compounds [59,60,[62][63][64]73]. In our laboratory, we focused on the synthesis of a thioether phospholipid (1-S-dodecyl-2-Odecyl-thioglycero-3-phosphatidic acid) conjugated to either gemcitabine or ara-C [75].…”

Section: Phospholipid Gemcitabine and Ara-c Conjugatesmentioning

confidence: 99%

Lipid Nucleoside Conjugates for the Treatment of Cancer

Richard¹,

Kucera²

2005

CPD

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Phospholipid nucleoside conjugates and nucleosides with chemical additions to the hydroxyl and amino moieties have been used since the 1970s in order to increase the biological activity of the parent compound. Previous investigators have found that adding lipid moieties to ara-C or chemically linking ara-C to a phospholipid creates a prodrug that exhibits superior cytotoxic activity compared to ara-C alone when used in animal tumor models. The novel ara-C molecules reveal different pharmacological profiles from the parent compound such as decreased catabolism by cytidine deaminase, increased plasma half-life, and release of nucleoside monophosphate, a reaction that bypasses the rate limiting initial nucleoside phosphorylation. Additionally, these compounds were able to penetrate the blood-brain barrier and were active against tumor cells implanted i.c. The purpose of this review is to briefly cover the history and successes of previous investigators who have synthesized and tested these phospholipid ara-C conjugates, to discuss recent phospholipid ara-C and fludarabine conjugates, and to discuss the synthetic design and synthesis of a novel phospholipid gemcitabine conjugate. These phospholipid nucleoside conjugates possess the potential to have superior anti-neoplastic cytotoxicity profiles with fewer side effects than the parent nucleoside and merit further investigation.

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“…Finally, phospholipid-linked AraC conjugates were also developed. Following enzymolysis, these prodrugs release the monophosphate form of AraC (32)(33)(34). Although the mechanism of increased efficacy is still unknown, it has been shown that they lead to a more prolonged intracellular retention of the triphosphate (active) form than the parent AraC drug.…”

Section: Tumor Targeting Of Anticancer Drugsmentioning

confidence: 99%

Lipid-Based Drug Carriers for Prodrugs to Enhance Drug Delivery

Zaro

2014

AAPS J

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ABSTRACT. The combination of lipid drug delivery systems with prodrugs offers several advantages including improved pharmacokinetics, increased absorption, and facilitated targeting. Lipidization and use of lipid carriers can increase the pharmacological half-life of the drug, thus improving pharmacokinetics and allowing less frequent dosing. Lipids also offer advantages such as increased absorption through the intestines for oral drug absorption and to the CNS for brain delivery. Furthermore, the use of lipid delivery systems can enhance drug targeting. Endogenous proteins bind lipids in the blood and carry them to the liver to enable targeting of this organ. Drugs with significant side effects in the stomach can be specifically delivered to enterocytes by exploiting lipases for prodrug activation. Finally, lipids can be used to target the lymphatic system, thus bypassing the liver and avoiding first-pass metabolism. Lymphatic targeting is also important for antiviral drugs in the protection of B and T lymphocytes. In this review, both lipid-drug conjugates and lipid-based carriers will be discussed. An overview, including the chemistry and assembly of the systems, as well as examples from the clinic and in development, will be provided.

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A Phospholipid Derivative of Cytosine Arabinoside and Its Conversion to Phosphatidylinositol by Animal Tissue

Cited by 55 publications

References 25 publications

Replica plating and in situ enzymatic assay of animal cell colonies established on filter paper.

Replica plating and in situ enzymatic assay of animal cell colonies established on filter paper.

Lipid Nucleoside Conjugates for the Treatment of Cancer

Lipid-Based Drug Carriers for Prodrugs to Enhance Drug Delivery

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