title: Synthesis and biological evaluation of spin-labeled alkylphospholipid analogs.
abstract: Alkylphospholipid analogues of perifosine and miltefosine bearing a nitroxide moiety at different positions on an alkyl chain were synthesized as electron paramagnetic resonance (EPR) probes. Their amphiphilic properties were characterized by determining their critical micelle concentration (cmc) and hemolytic activity on erythrocytes both in free and liposomal form. Spin-labeled analogues as membrane components of large unilamellar liposomes containing cholesterol and dicetyl phosphate or in free solution were evaluated using the MTT assay to determine growth inhibition on MT1, MT3, and MCF7 breast cancer cell lines. 4a (IC50 = 56.4 microM) was found to be significantly more active than the perifosine against the MCF-7 cell line. Its high cmc (194.03 microM) and low hemolytic activity shows that its cytotoxic activity might be more specific; therefore, 4a can be an important molecular tool for further EPR investigations.
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Askerceva 7, SI-1000 Ljubljana, Slovenia. janez.mravljak@ffa.uni-lj.si
authors.forename: Janez
authors.initials: J
authors.lastname: Mravljak
authors.forename: Reiner
authors.initials: R
authors.lastname: Zeisig
authors.forename: Slavko
authors.initials: S
authors.lastname: Pecar
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D003497:Cyclic N-Oxides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006461:Hemolysis; D006801:Humans; D008081:Liposomes; D008823:Micelles; D010755:Organophosphates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010743:Phospholipids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012996:Solutions; D013113:Spin Labels / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C505560:4-((((13-(2-butyl-3-oxyl-4,4-dimethyl-1,3-oxazolidine-2-yl)tridecyl)oxy)(oxy)phosphoryl)oxy)-1,1-dimethylpiperidinium; D000970:Antineoplastic Agents; D003497:Cyclic N-Oxides; D008081:Liposomes; D008823:Micelles; D010755:Organophosphates; D010743:Phospholipids; D012996:Solutions; D013113:Spin Labels; D013501:Surface-Active Agents; D010767:Phosphorylcholine; C105905:perifosine; C039128:miltefosine