2-hydroxyethyl Amino Research Articles

Effect of Cationic Lipid Type in Folate-PEG-Modified Cationic Liposomes on Folate Receptor-Mediated siRNA Transfection in Tumor Cells.

In this study, we examined the effect of cationic lipid type in folate (FA)-polyethylene glycol (PEG)-modified cationic liposomes on gene-silencing effects in tumor cells using cationic liposomes/siRNA complexes (siRNA lipoplexes). We used three types of cationic cholesterol derivatives, cholesteryl (3-((2-hydroxyethyl)amino)propyl)carbamate hydroiodide (HAPC-Chol), N-(2-(2-hydroxyethylamino)ethyl)cholesteryl-3-carboxamide (OH-Chol), and cholesteryl (2-((2-hydroxyethyl)amino)ethyl)carbamate (OH-C-Chol), and we prepared three types of FA-PEG-modified siRNA lipoplexes. The modification of cationic liposomes with 1–2 mol % PEG-lipid abolished the gene-silencing effect in human nasopharyngeal tumor KB cells, which overexpress the FA receptor (FR). In contrast, FA-PEG-modification of cationic liposomes restored gene-silencing activity regardless of the cationic lipid type in cationic liposomes. However, the optimal amount of PEG-lipid and FA-PEG-lipid in cationic liposomes for selective gene silencing and cellular uptake were different among the three types of cationic liposomes. Furthermore, in vitro transfection of polo-like kinase 1 (PLK1) siRNA by FA-PEG-modified liposomes exhibited strong cytotoxicity in KB cells, compared with PEG-modified liposomes; however, in in vivo therapy, intratumoral injection of PEG-modified PLK1 siRNA lipoplexes inhibited tumor growth of KB xenografts, as well as that of FA-PEG-modified PLK1 siRNA lipoplexes. From these results, the optimal formulation of PEG- and FA-PEG-modified liposomes for FR-selective gene silencing might be different between in vitro and in vivo transfection.

SiRNA delivery into tumor cells by cationic cholesterol derivative-based nanoparticles and liposomes.

Previously, we reported that cationic nanoparticles (NP) composed of diamine-type cholesteryl-3-carboxamide (OH-Chol, N-(2-(2-hydroxyethylamino)ethyl)cholesteryl-3-carboxamide) and Tween 80 could deliver small interfering RNA (siRNA) with high transfection efficiency into tumor cells. In this study, we synthesized new diamine-type cationic cholesteryl carbamate (OH-C-Chol, cholesteryl (2-((2-hydroxyethyl)amino)ethyl)carbamate) and triamine-type carbamate (OH-NC-Chol, cholesteryl (2-((2-((2-hydroxyethyl)amino)ethyl)amino)ethyl)carbamate), and prepared cationic nanoparticles composed of OH-C-Chol or OH-NC-Chol with Tween 80 (NP-C and NP-NC, respectively), as well as cationic liposomes composed of OH-C-Chol or OH-NC-Chol with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) (LP-C and LP-NC, respectively) for evaluation of their possible use as siRNA delivery vectors. LP-C and LP-NC/siRNA complexes (lipoplexes) exhibited larger gene silencing effects than NP-C and NP-NC/siRNA complexes (nanoplexes), respectively, in human breast tumor MCF-7 cells, although the NP-C nanoplex showed high association with the cells. In particular, LP-NC lipoplex could induce strong gene suppression, even at a concentration of 5 nM siRNA. From these results, cationic liposomes composed of OH-NC-Chol and DOPE may have potential as gene vectors for siRNA transfection to tumor cells.

N-(2-hydroxyethyl)-ethylenediamine-based ionic liquids: Synthesis, structural characterization, thermal, dielectric and catalytic properties

Three novel acetate and formate ammonium salts of N-(2-hydroxyethyl)-ethylenediamine (Hydeten) were synthesized as room temperature ionic liquids (RTILs) {2-(2-hydroxy ethylamino)-ethanaminium formate (IL1a), 2-amino-N-(2-hydroxyethyl)-ethanaminium formate (IL1b), and 2-(2-hydroxyethylamino)-ethanaminium acetate (IL2)}. Their structures were characterized by using elemental analysis, FT-IR, 1H and 13C NMR techniques. Some thermal properties of these ILs were determined by using TG and DSC techniques. Real dielectric (ε′)-frequency (ω), imaginary dielectric (ε″)-frequency (ω), and conductivity (σAC)-frequency (ω) relationships of IL1a–b, IL2, and doped IL1–2 were investigated. These ILs were also tested as solvent or catalyst in the synthesis of some organic compounds.

Synthesis and Preliminary Biological Activity of Some New Pyrazole Derivatives as Acyclonucleoside Analogues

Some novel pyrazole acyclonucleosides were prepared through binding of pyrazole-3,5-substituted derivatives with acyclic substituents mimetizing individual fragments of the ribose ring such as: 1-[(2-hydroxyethoxy) methyl], 1-[4-(hydroxybutyl)], 1-[3- (hydroxypropyl)] and 1-[(2-hydroxyethyl amino) methyl]. Their syntheses were performed from easily accessible starting materials. The prepared compounds were evaluated for their antibacterial activity. Structure-activity relationship studies (SAR) indicate that introduction of modified arm in N1 position of pyrazole moieties has not any impact on the biolgical activity. Keywords: Pyrazole, Acyclonucleoside, Synthesis, Biological activity