0000000000116541
AUTHOR
Marina Gosteva
Studies of the physicochemical and structural properties of self-assembling cationic pyridine derivatives as gene delivery agents.
New amphiphilic pyridine derivatives containing dodecyloxycarbonyl substituents at positions 3 and 5 and cationic moieties at positions 2 and 6 have been designed and synthesised. Compounds of this type can be considered as synthetic lipids. The corresponding 1,4-dihydropyridine (1,4-DHP) derivatives have earlier been proposed as a promising tool for plasmid DNA (pDNA) delivery in vitro. In this work studies of the self-assembling properties of amphiphilic pyridine derivatives leading to the formation of liposomes, determination of particle size, zeta-potential and critical micelle concentration (CMC) with dynamic light scattering (DLS) measurements are described. Furthermore, thermal analy…
Synthesis and studies of calcium channel blocking and antioxidant activities of novel 4-pyridinium and/or N-propargyl substituted 1,4-dihydropyridine derivatives
The novel 1,4-dihydropyridine derivatives containing the cationic pyridine moiety at the position 4, and the N-propargyl group as a substituent at position 1 of the 1,4-DHP cycle were designed, synthesised, and assessed in biological tests. Among all the novel compounds, the 4-(N-dodecyl) pyridinium group-containing compounds 11 (without the N-propargyl group) and 12 (with the N-propargyl group) demonstrated the highest calcium antagonistic properties against neuroblastoma SH-SY5Y (IC50 about 5–14 mM) and the vascular smooth muscle A7r5 cell (IC50 – 0.6–0.7 mM) lines, indicating that they predominantly target the L-type calcium channels. These compounds showed a slight total antioxidant act…
Evaluation of Antiradical Activity and Reducing Capacity of Synthesised Bispyridinium Dibromides Obtained by Quaternisation of 4-Pyridyl-1,4-dihydropyridines with Propargyl Bromide
New bispyridinium dibromides based on the 1,4-dihydropyridine (1,4-DHP) cycle were synthesised in the reaction between 4-pyridyl-1,4-DHP derivatives and propargyl bromide. It has been shown that variation of the substituent position on the pyridine as well as small changes in the electronic nature of the 1,4-DHP cycle as a result of the substituent nature at the 3 and 5 positions do not affect the course of the reaction and in all cases the corresponding bispyridinium dibromides 4a–e were formed. The antiradical activity, using 1,1-diphenyl-2-picrylhydrazine as a free radical scavenger, and the reducing capacity using phosphomolybdenum complexes have been evaluated for the newly synthesise…
Studies of Preparation and Stability of Liposomes Formed by 1,1'-[(3,5-didodeciloxycarbonyl-4-phenyl-1,4-dihydropyridine-2,6-diil)-dimethylen]Bispyridinium Dibromide
In this work we describe the studies of preparation and stability of liposomes formed by 1,1'-[(3,5-didodeciloxycarbonyl-4-phenyl-1,4-dihydropyridine-2,6-diil) dimethylebispyridinium dibromide, novel lipid-like compound. The influence of the amount of amphiphilic compound, solvent and sonication time was studied. Liposomes were prepared by dispersing of compound in the corresponding media at a selected concentration by sonication using a probe type sonicator and characterised by atomic force microscopy (AFM) and dynamic light scattering (DLS) methods.
Gene delivery agents possessing antiradical activity: self-assembling cationic amphiphilic 1,4-dihydropyridine derivatives
Seventeen 1,4-dihydropyridine (1,4-DHP) amphiphiles including differently substituted pyridinium, pyrazinium, N-methyl piperidinium or N-methyl morpholinium moieties as the cationic head-group of the molecule have been designed and synthesised. 1,4-DHP amphiphiles have been earlier proposed as a promising tool for plasmid DNA (pDNA) delivery in vitro. In this work the ability of the 1,4-DHP amphiphiles to self-assemble, to bind pDNA and to transfer it into the cells as well as the cytotoxicity of 1,4-DHP amphiphiles–pDNA complexes was studied. Furthermore, antiradical activity (ARA) of the 1,4-DHP derivatives was determined. We have revealed that all new 1,4-DHP amphiphiles possessed self-a…
CCDC 978170: Experimental Crystal Structure Determination
Related Article: Martins Rucins, Marina Gosteva, Sergey Belyakov, Arkadij Sobolev , Karlis Pajuste, Mara Plotniece, Brigita Cekavicus, Dace Tirzite, Aiva Plotniece|2015|Aust.J.Chem.|68|86|doi:10.1071/CH14033