ABSTRACT
Mutagenic activity of non-phosphorous cationic alkyl glycerolipid rac-N-{4-[(2-Methoxy-3-octadecyloxy)propyl]oxycarbonylbutyl}-N,N-dimethyl-N-(2-hydroxyethyl) ammonium iodide was evaluated. According performed Ames assay results indicated on non-mutagenic properties tested compound. Resulting data open the possibility to carry out biological study in vivo for class of ether cationic glycerolipids and further applications as a potential agent of anticancer therapy.
Subject(s)
Antineoplastic Agents , Glycolipids , Mutagenesis/drug effects , Salmonella typhimurium/genetics , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Drug Screening Assays, Antitumor , Glycolipids/chemistry , Glycolipids/pharmacology , Salmonella typhimurium/growth & development , Salmonella typhimurium/metabolismABSTRACT
Synthesis of new antitumor ether glycerolipids with various heterocyclic nitrogen-containing bases as polar domains is described. We propose synthetic scheme for cationic lipids containing aliphatic short-chain substituents in the heterocyclic polar head.
Subject(s)
Antineoplastic Agents/chemical synthesis , Ether/chemical synthesis , Glycolipids/chemical synthesis , Nitrogen/chemistry , Ether/chemistry , Glycolipids/chemistry , Heterocyclic Compounds/chemistry , Humans , Magnetic Resonance Spectroscopy , Mass Spectrometry/methodsABSTRACT
Amino analogues of cholic acid were synthesized by reduction of oximes with combination of titanium(III) chloride and sodium cyanoborohydride.
Subject(s)
Amines/chemical synthesis , Cholates/chemical synthesis , Amines/chemistry , Borohydrides/chemistry , Cholates/chemistry , Hydroxides/chemistry , Oximes/chemistry , Titanium/chemistryABSTRACT
In this study, we synthesized a new galactosylated cationic lipid and investigated its biological activity. The structure of lipid combines both spermine residue for DNA compaction and galactose moiety for the improvement of aggregation behavior of lipoplexes. Lipid was low toxic for different mammalian cells, and was able both to compact plasmid DNA and to mediate cellular accumulation of various nucleic acids (ODN, pDNA and siRNA) exhibiting biological activity (transgene expression, gene silencing).
Subject(s)
Galactose/chemistry , Lipids/chemical synthesis , Polyamines/chemistry , Animals , Cell Line , Cell Survival/drug effects , Cricetinae , Flow Cytometry , Gene Transfer Techniques , Humans , Lipids/chemistry , Lipids/toxicity , Liposomes/chemistry , Microscopy, Atomic Force , Molecular Structure , Polyelectrolytes , TransfectionABSTRACT
The review is summarizes current information on biological activity and search of the antineoplastic mechanism of action of alkyl glycerolipids. Special attention is paid to following problems: selective ability phosphorus alkyl glycerolipids, antineoplastic activity, cytostatic and cytotoxic effects of edelfosine and its analogues. The review contains set of the data known for today from the literature, on the possible mechanism cytoyoxic actions of such connections.
Subject(s)
Antineoplastic Agents/pharmacology , Phospholipid Ethers/pharmacology , Animals , Antineoplastic Agents/chemistry , Caspases/physiology , Cell Death , Humans , Membrane Microdomains/physiology , Phospholipid Ethers/chemistry , Receptors, Tumor Necrosis Factor/physiology , Signal Transduction , fas Receptor/physiologyABSTRACT
An approach to synthesis of cationic carbohydrate surfactants with potential antimicrobial or transfected activities is described.
Subject(s)
Galactose/chemistry , Surface-Active Agents/chemical synthesis , Cations , Molecular Structure , Solvents , Surface-Active Agents/chemistryABSTRACT
A series of new modifications of alkyl cationic glycerolipids with hetero polar domain has been synthesized. The most active compound rac-N-(4-[(2-ethoxy-3-octadecyloxy)prop-1-yloxycarbonyl]butyl)-N'-etylimidazoliyiodid in micromolar concentrations causes a delay of cell cycle in phase G1, DNA fragmentation and apoptosis of cell line leukemia.
Subject(s)
Apoptosis/drug effects , DNA Fragmentation/drug effects , G1 Phase/drug effects , Glycerides , Heterocyclic Compounds , Leukemia/metabolism , Glycerides/chemical synthesis , Glycerides/chemistry , Glycerides/pharmacology , Heterocyclic Compounds/chemical synthesis , Heterocyclic Compounds/chemistry , Heterocyclic Compounds/pharmacology , Humans , K562 Cells , Leukemia/drug therapyABSTRACT
The synthesis of cationic lipids on the basis of 1,2-di-O-tetradecylglycerol is described. The cationic groups represented by the residues of nitrogen-containing heterocyclic bases are attached to the diglyceride backbone through O,O- and N,O-acetal bonds. The resulting lipids can be used as nonviral gene delivery systems to eukaryotic cells.
Subject(s)
Diglycerides/chemistry , Diglycerides/chemical synthesis , Transfection , CationsABSTRACT
The paper provides the synthesis of new phosphorless glycerolipids with an ether bond that contain heterocyclic bases in the polar domain. The physico-chemical characteristics and biological activity of the prepared compounds were studied.
Subject(s)
Glycerides/chemical synthesis , Glycerides/pharmacology , Heterocyclic Compounds/chemical synthesis , Heterocyclic Compounds/pharmacology , Glycerides/chemistry , Heterocyclic Compounds/chemistry , Humans , K562 Cells , U937 CellsABSTRACT
Modified series of phosphorusless edelfosine analogues bearing the polar heads of aliphatic bases, N,N-dimethylethanolamine and N,N,N(1),N(1)-tetramethylethylenediamine, were synthesized, with the length of the spacer varying from three to four methylene units. The cytotoxic characteristics of the compounds synthesized were studied.
Subject(s)
Deanol/chemical synthesis , Ethylenediamines/chemical synthesis , Phospholipid Ethers/chemical synthesis , Deanol/chemistry , Ethylenediamines/chemistry , Phospholipid Ethers/chemistryABSTRACT
A convenient approach to the synthesis of mono- and polycationic glycolipid amphiphiles is suggested. The compounds obtained can be used for study of the structure-activity relationship and determination of the effect of hydrophobic and cationic domains on transfection efficiency.
Subject(s)
Glycolipids/chemistry , Polyamines/chemistry , Transfection , Acylation , Animals , Carbohydrates/chemical synthesis , Carbohydrates/chemistry , Glycolipids/chemical synthesis , Liposomes/chemistry , Polyamines/chemical synthesis , PolyelectrolytesABSTRACT
This review focuses on the synthesis and mechanisms of antitumor activity of cationic non-phosphorus analogs of edelfosine. The role of variable length and mode of conjugation of the spacer group, the types of cationic 'head', and the length of the substituent at C2 atom of the glycerol backbone are discussed, providing the basis for rational design of lipophilic anticancer drugs, in particular, for elimination of multidrug resistant cells.
Subject(s)
Antineoplastic Agents/pharmacology , Lipids/pharmacology , Antineoplastic Agents/chemistry , Cations , Lipids/chemistry , Molecular Structure , Phosphorus/chemistry , Structure-Activity RelationshipABSTRACT
A number of alkyl glycerolipids with short-chain substituents at the C2 atom of glycerol and functional groups (carboxy and amino) in the polar head were synthesized. Cationic alkyl glycerolipids with a hydroxyl function in the hydrophilic moiety were also obtained. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 5; see also http: // www.maik.ru.
Subject(s)
Biochemistry/methods , Glycerol/chemistry , Lipids/chemistry , Cations , Glycerol/chemical synthesis , Lipids/chemical synthesis , Protein Structure, TertiaryABSTRACT
Cationic derivatives of deoxycholic acid with N,N-dimethylenediamine, epsilon-aminocaproic acid, and pyridine as polar heads were synthesized. The cationic groups were linked to 3alpha- and 12alpha-hydroxy groups of the steroid moiety through ester or urethane bonds. Liposomal formulations of the compounds synthesized may be used for gene delivery in cells. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 5; see also http: //www.maik.ru.
Subject(s)
Biochemistry/methods , Deoxycholic Acid/chemistry , Liposomes/chemistry , Cations , Liposomes/chemical synthesis , Magnetic Resonance Spectroscopy , Molecular StructureABSTRACT
A glucosyldiglyceride containing residues of 11-aminoundecanoic acid was synthesized for constructing pH-sensitive liposomes.
Subject(s)
Biochemistry/methods , Glycolipids/chemical synthesis , Liposomes , Glucose/chemistry , Glycerides/chemistry , Glycolipids/chemistry , Hydrogen-Ion Concentration , Liposomes/chemical synthesis , Liposomes/chemistry , Magnetic Resonance Spectroscopy , Molecular StructureABSTRACT
Sensitivity of 293 human epithelial kidney cells transfected by human cytochrome CYP450 gene to cyclophosphamide was investigated. Transfection was carried out by plasmid DNA containing CYP2B6 gene complexed with cationic liposomes. Liposomes were prepared from mixture of cationic lipids and cholesterol at different molar ratios. Experimental protocol included the following steps: transfection of epithelial kidney cells by complexes of plasmid DNA-cationic liposomes, clone selection in the medium with antibiotic Geneticin G418, selected clone harvesting and their treatment by cyclophosphamide as following cytotoxicity evaluation. It was shown that addition of 0.25 mM of cyclophosphamide resulted in death of 40-45% transfected cell population.
Subject(s)
Antineoplastic Agents, Alkylating/pharmacology , Aryl Hydrocarbon Hydroxylases/genetics , Cyclophosphamide/pharmacology , Epithelial Cells/drug effects , Oxidoreductases, N-Demethylating/genetics , Transfection , Cations , Cell Line , Cell Survival/drug effects , Cytochrome P-450 CYP2B6 , Drug Tolerance , Humans , Kidney/cytology , LiposomesABSTRACT
1,3-Dioxolane series cationic lipids containing residues of aliphatic or heterocyclic nitrogenous bases were synthesized. The bases were attached to the glycerol backbone either directly (piperazine) or via a spacer group through a thioether bond.
Subject(s)
Heterocyclic Compounds/chemical synthesis , Lipids/chemical synthesis , Cations , Dioxolanes/chemistry , Fatty Acids/chemistry , Glycerol/chemistryABSTRACT
A number of cationic derivatives of cholesterol containing polar residues of N-methylimidazole, pyridine, N-methylmorpholine, and 4-N,N-dimethyaminopyridine were synthesized by the interaction of the corresponding heterocyclic bases with cholesterol 5-bromopentanoate followed by the treatment with methyl iodide in the case of tertiary amines. In addition, N-(4-cholesteryloxycarbonylbutyl)piperazine was obtained for the preparation of pH-sensitive liposomes.
Subject(s)
Cholesterol/chemistry , Heterocyclic Compounds/chemistry , Cations , Magnetic Resonance Spectroscopy , Mass Spectrometry , Spectrophotometry, InfraredABSTRACT
A series of glucosyl dialkylglycerols with the pyridinium, N-morpholinium, and N-methylimidazolium polar heads were synthesized by quaternization of the corresponding bases with the acetylated glucosyl diglyceride 6-O-methane- and 6-O-toluenesulfonates. The resulting compounds were designed for the use in gene delivery systems.