Synthesis and Evaluation of Antitumor Alkylphospholipid Prodrugs

Autor: Françoise Pons, Boris Gaillard, Luc Lebeau, Jean-Serge Remy
Přispěvatelé: Conception et application de molécules bioactives (CAMB), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie des Systèmes Fonctionnels, Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
hemolytic toxicity
Pharmaceutical Science
02 engineering and technology
[CHIM.THER]Chemical Sciences/Medicinal Chemistry
Pharmacology
alkylphospholipid
030226 pharmacology & pharmacy
chemistry.chemical_compound
0302 clinical medicine
Drug Stability
immune system diseases
Neoplasms
Prodrugs
Pharmacology (medical)
Cytotoxicity
ComputingMilieux_MISCELLANEOUS
Prodrug
[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences
021001 nanoscience & nanotechnology
Perifosine
Organophosphates
Hemolysis
3. Good health
Toxicity
Molecular Medicine
Administration
Intravenous
perifosine
prodrug
0210 nano-technology
miltefosine
Biotechnology
medicine.drug
Maximum Tolerated Dose
Side effect
Phosphorylcholine
erufosine
Antineoplastic Agents
03 medical and health sciences
Cell Line
Tumor
Membrane activity
medicine
Humans
neoplasms
Miltefosine
Organic Chemistry
medicine.disease
Quaternary Ammonium Compounds
chemistry
Drug Screening Assays
Antitumor
Zdroj: Pharmaceutical Research
Pharmaceutical Research, American Association of Pharmaceutical Scientists, 2020, 37 (6), pp.106. ⟨10.1007/s11095-020-02830-y⟩
Pharmaceutical Research, American Association of Pharmaceutical Scientists, 2020, 37 (6), ⟨10.1007/s11095-020-02830-y⟩
ISSN: 0724-8741
1573-904X
DOI: 10.1007/s11095-020-02830-y⟩
Popis: International audience; Purpose Hemolysis is a serious side effect of antitumor alkylphospholipids (APLs) that limits dose levels and is a constraint in their use in therapeutic regimen. Nine prodrugs of promising APLs (miltefosine, perifosine, and erufosine) were synthesized so as to decrease their membrane activity and improve their toxicity profile while preserving their antineoplastic potency. Methods The synthesis of the pro-APLs was straightforwardly achieved in one step starting from the parent APLs. The critical aggregation concentration of the prodrugs, their hydrolytic stability under various pH conditions, their blood compatibility and cytotoxicity in three different cell lines were determined and compared to those of the parent antitumor lipids. Results The APL prodrugs display antitumor activity which is similar to that of the parent alkylphospholipids but without associated hemolytic toxicity. Conclusion The pro-APL compounds may be considered as intravenously injectable derivatives of APLs. They could thus address one of the major issues met in cancer therapies involving antitumor lipids and restricting their utilization to oral and topical administration because of limited maximum tolerated dose.
Databáze: OpenAIRE
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