scholarly journals Contribution of Molecular Structure to Self-Assembling and Biological Properties of Bifunctional Lipid-Like 4-(N-Alkylpyridinium)-1,4-Dihydropyridines

Pharmaceutics ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 115 ◽  
Author(s):  
Martins Rucins ◽  
Pavels Dimitrijevs ◽  
Klavs Pajuste ◽  
Oksana Petrichenko ◽  
Ludmila Jackevica ◽  
...  
Keyword(s):  
Chain Length ◽  
Alkyl Chain ◽  
Hydrophobic Interactions ◽  
Biological Activities ◽  
Biological Properties ◽  
Alkyl Chain Length ◽  
Critical Aggregation Concentration ◽  
Self Assembling ◽  
Basal Cytotoxicity

The design of nanoparticle delivery materials possessing biological activities is an attractive strategy for the development of various therapies. In this study, 11 cationic amphiphilic 4-(N-alkylpyridinium)-1,4-dihydropyridine (1,4-DHP) derivatives differing in alkyl chain length and propargyl moiety/ties number and position were selected for the study of their self-assembling properties, evaluation of their cytotoxicity in vitro and toxicity on microorganisms, and the characterisation of their interaction with phospholipids. These lipid-like 1,4-DHPs have been earlier proposed as promising nanocarriers for DNA delivery. We have revealed that the mean diameter of freshly prepared nanoparticles varied from 58 to 513 nm, depending upon the 4-(N-alkylpyridinium)-1,4-DHP structure. Additionally, we have confirmed that only nanoparticles formed by 4-(N-dodecylpyridinium)-1,4-DHP derivatives 3 and 6, and by 4-(N-hexadecylpyridinium)-1,4-DHP derivatives 10 and 11 were stable after two weeks of storage. The nanoparticles of these compounds were found to be homogenous in size distribution, ranging from 124 to 221 nm. The polydispersity index (PDI) values of 1,4-DHPs samples 3, 6, 10, and 11 were in the range of 0.10 to 0.37. We also demonstrated that the nanoparticles formed by 4-(N-dodecylpyridinium)-1,4-DHP derivatives 3, 6, and 9, and 4-(N-hexadecylpyridinium)-1,4-DHP derivatives 10 and 11 had zeta-potentials from +26.07 mV (compound 6) to +62.80 mV (compound 11), indicating a strongly positive surface charge and confirming the relative electrostatic stability of these nanoparticle solutions. Transmission electron microscopy (TEM) images of nanoaggregates formed by 1,4-DHPs 3 and 11 confirmed liposome-like structures with diameters around 70 to 170 nm. The critical aggregation concentration (CAC) value interval for 4-(N-alkylpyridinium)-1,4-DHP was from 7.6 µM (compound 11) to 43.3 µM (compound 6). The tested 4-(N-alkylpyridinium)-1,4-DHP derivatives were able to quench the fluorescence of the binary 1,6-diphenyl-1,3,5-hexatriene (DPH)—1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) system, demonstrating hydrophobic interactions of 1,4-DHPs with phospholipids. Thus, 4-(N-dodecylpyridinium)-1,4-DHP derivative 3 quenched the fluorescence of the DPH–DPPC system more efficiently than the other 4-(N-alkylpyridinium)-1,4-DHP derivatives. Likewise the compound 3, also 4-(N-dodecylpyridinium)-1,4-DHP derivative 9 interacted with the phospholipids. Moreover, we have established that increasing the length of the alkyl chain at the quaternised nitrogen of the 4-(N-alkylpyridinium)-1,4-DHP molecule or the introduction of propargyl moieties in the 1,4-DHP molecule significantly influences the cytotoxicity on HT-1080 (human fibrosarcoma) and MH-22A (mouse hepatocarcinoma) cell lines, as well as the estimated basal cytotoxicity. Additionally, it was demonstrated that the toxicity of the 4-(N-alkylpyridinium)-1,4-DHP derivatives on the Gram-positive and Gram-negative bacteria species and eukaryotic microorganism depended on the presence of the alkyl chain length at the N-alkyl pyridinium moiety, as well as the number of propargyl groups. These lipid-like compounds may be proposed for the further development of drug formulations to be used in cancer treatment.

scholarly journals Acyl and alkyl chain length of GPI-anchors is critical for raft association in vitro

FEBS Letters ◽  
1999 ◽  
Vol 462 (1-2) ◽  
pp. 47-50 ◽  
Author(s):  
Jürgen Benting ◽  
Anton Rietveld ◽  
Iris Ansorge ◽  
Kai Simons
Keyword(s):  
Chain Length ◽  
Alkyl Chain ◽  
Alkyl Chain Length

scholarly journals In vitro Analysis of the Effect of Alkyl-Chain Length of Anionic Surfactants on the Skin by Using a Reconstructed Human Epidermal Model

2014 ◽  
Vol 63 (10) ◽  
pp. 995-1004 ◽  
Author(s):  
Fumiko Yamaguchi ◽  
Shin-ichi Watanabe ◽  
Fusae Harada ◽  
Miyuki Miyake ◽  
Masaki Yoshida ◽  
...  
Keyword(s):  
Chain Length ◽  
Alkyl Chain ◽  
Anionic Surfactants ◽  
Alkyl Chain Length ◽  
Vitro Analysis ◽  
In Vitro Analysis

scholarly journals Further studies on the substrate specificity and inhibition of the stereospecific CS2 secondary alkylsulphohydrolase of Comamonas terrigena

1980 ◽  
Vol 191 (2) ◽  
pp. 467-473 ◽  
Author(s):  
Carol H. Barrett ◽  
Kenneth S. Dodgson ◽  
Graham F. White
Keyword(s):  
Free Energy ◽  
Chain Length ◽  
Alkyl Chain ◽  
Hydrophobic Interactions ◽  
Standard Free Energy ◽  
Alkyl Chain Length ◽  
Alkyl Sulphate ◽  
Competitive Inhibitors ◽  
Free Energy Of Binding ◽  
Comamonas Terrigena

A series of d-alkan-2-yl sulphate esters (C7–C14) were prepared by sulphation of the resolved parent alcohols by a method that entails complete retention of configuration. These sulphate esters were tested as substrates for the stereospecific CS2 secondary alkylsulphohydrolase of Comamonas terrigena. Vmax. reached a maximum with the C9 compound, whereas logKm decreased linearly as the alkyl-chain length was increased from C7 to C14. A parallel series of l-alkan-2-yl sulphates was also prepared, and these esters, together with homologous series of primary alkyl sulphates and primary alkanesulphonates, were shown to be competitive inhibitors of the CS2 enzyme. For each series of compounds, logKi values decreased linearly with increasing alkyl-chain length. Plots of chain length against the standard free energy of binding (ΔG0) of substrate and inhibitors to the CS2 enzyme showed that the standard free energy of association of a –CH2– group with the enzyme was 2.0–2.4kJ/mol for all classes of compound studied, indicating an important contribution from hydrophobic interactions to the overall binding. Plots for d-alkan-2-yl sulphate substrates and primary alkyl sulphate inhibitors were nearly coincident, suggesting that the overall interaction between a primary ester and the enzyme is the same as that between the isomeric secondary substrate and the enzyme. Plots for l-alkan-2-yl sulphate and alkanesulphonate inhibitors were very similar to each other, but were displaced by 1.5–3.0kJ/mol from that for substrate binding. This indicates that the binding of any one of these particular inhibitors involves one carbon atom fewer than the number involved in binding a substrate of the same chain length. These observations are discussed in terms of a three-point attachment of substrate to the enzyme involving the alkyl chain, sulphate group and the C-1 methyl group.

O-Alkyl dioleoylphosphatidylcholinium Compounds:  The Effect of Varying Alkyl Chain Length on Their Physical Properties and in Vitro DNA Transfection Activity

2000 ◽  
Vol 11 (3) ◽  
pp. 306-313 ◽  
Author(s):  
Howard S. Rosenzweig ◽  
Vera A. Rakhmanova ◽  
Thomas J. McIntosh ◽  
Robert C. MacDonald
Keyword(s):  
Physical Properties ◽  
Chain Length ◽  
Alkyl Chain ◽  
Alkyl Chain Length ◽  
Dna Transfection

Alkoxy propane prodrugs of foscarnet: effect of alkyl chain length on in vitro antiviral activity in cells infected with HIV-1, HSV-1 and HCMV

1997 ◽  
Vol 36 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Ganesh D Kini ◽  
James R Beadle ◽  
Hong Xie ◽  
Kathy A Aldern ◽  
Douglas D Richman ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Chain Length ◽  
Alkyl Chain ◽  
Alkyl Chain Length ◽  
Hiv 1 ◽  
In Cells ◽  
Hsv 1

In silico and in vitro studies of Imidazolium ionic liquids as effective antibacterial agents against multidrug resistant Escherichia coli strains

2020 ◽  
Vol 16 ◽  
Author(s):  
Diana Hodyna ◽  
Vasyl Kovalishyn ◽  
Ivan Semenyuta ◽  
Volodymyr Blagodatny ◽  
Sergiy Rogalsky ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibacterial Activity ◽  
Ionic Liquids ◽  
Chain Length ◽  
Active Site ◽  
Alkyl Chain ◽  
Multidrug Resistant ◽  
Alkyl Chain Length ◽  
E Coli

Background: Escherichia coli especially its multiresistant strains as the common foodborne pathogens cause blood stream infections, nosocomial pneumonia, infections of the skin and soft tissues. Therefore, the search for new effective biologically active compounds has been rapidly increasing in recent few decades. In this paper, we describe Quantitative Structure-Activity Relationships (QSAR) studies, molecular docking and in vitro antibacterial activity evaluation of series imidazolium-based ionic liquids (ILs) against E. coli spp. Methods: 2D fragment-based, classification and regression QSAR models were created using machine learning methods and types of descriptors via the OCHEM server. Biological testing of series of synthesized imidazolium ILs with predicted activity was performed by disc diffusion method. The most typical structures of symmetric and asymmetric ILs with high anti-E.coli activity (1e, 1h) were docked into the active site of enoylacyl carrier protein reductase (ENR) in E. coli. Results: Symmetric imidazolium ILs with C8 alkyl chain length demonstrated the highest antibacterial activity in comparison to the high antibacterial potential of asymmetric ILs with C12 alkyl chain length against drug-sensitive and drug-resistant E. coli strains including hemolytic E. coli. It should be noted that symmetric ILs with C6 or C9 alkyl chain length have the slightly lower activity against certain E. coli strains. The key role in the binding of compounds (1e, 1h) in the E. coli ENR active site associated with the NAD molecule and the amino acid residue Tyr146. Conclusion: The highly active symmetric and asymmetric imidazolium ILs can be considered as promising drug-candidates effective against E. coli spp. pathogens including multidrug resistant strains.

Tamarix articulata (T. articulata) - An Important Halophytic Medicinal Plant with Potential Pharmacological Properties

2019 ◽  
Vol 20 (4) ◽  
pp. 285-292 ◽  
Author(s):  
Abdullah M. Alnuqaydan ◽  
Bilal Rah
Keyword(s):  
Medicinal Plant ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Biological Properties ◽  
In Vivo Model ◽  
Drug Candidate ◽  
Phytochemical Analysis ◽  
Pharmacological Properties

Background:Tamarix Articulata (T. articulata), commonly known as Tamarisk or Athal in Arabic region, belongs to the Tamaricaece species. It is an important halophytic medicinal plant and a good source of polyphenolic phytochemical(s). In traditional medicines, T. articulata extract is commonly used, either singly or in combination with other plant extracts against different ailments since ancient times.Methods:Electronic database survey via Pubmed, Google Scholar, Researchgate, Scopus and Science Direct were used to review the scientific inputs until October 2018, by searching appropriate keywords. Literature related to pharmacological activities of T. articulata, Tamarix species, phytochemical analysis of T. articulata, biological activities of T. articulata extracts. All of these terms were used to search the scientific literature associated with T. articulata; the dosage of extract, route of administration, extract type, and in-vitro and in-vivo model.Results:Numerous reports revealed that T. articulata contains a wide spectrum of phytochemical(s), which enables it to have a wide window of biological properties. Owing to the presence of high content of phytochemical compounds like polyphenolics and flavonoids, T. articulata is a potential source of antioxidant, anti-inflammatory and antiproliferative properties. In view of these pharmacological properties, T. articulata could be a potential drug candidate to treat various clinical conditions including cancer in the near future.Conclusion:In this review, the spectrum of phytochemical(s) has been summarized for their pharmacological properties and the mechanisms of action, and the possible potential therapeutic applications of this plant against various diseases discussed.

scholarly journals Silver Nanoparticles Stabilized with Phosphorus-Containing Heterocyclic Surfactants: Synthesis, Physico-Chemical Properties, and Biological Activity Determination

Nanomaterials ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1883
Author(s):  
Martin Pisárčik ◽  
Miloš Lukáč ◽  
Josef Jampílek ◽  
František Bilka ◽  
Andrea Bilková ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Biological Activity ◽  
Zeta Potential ◽  
Chain Length ◽  
Alkyl Chain ◽  
Chemical Properties ◽  
Alkyl Chain Length ◽  
Microbial Pathogens ◽  
Physico Chemical ◽  
Phosphorus Containing

Phosphorus-containing heterocyclic cationic surfactants alkyldimethylphenylphospholium bromides with the alkyl chain length 14 to 18 carbon atoms were used for the stabilization of silver nanodispersions. Zeta potential of silver nanodispersions ranges from +35 to +70 mV, which indicates the formation of stable silver nanoparticles (AgNPs). Long-chain heptadecyl and octadecyl homologs of the surfactants series provided the most intensive stabilizing effect to AgNPs, resulting in high positive zeta potential values and smaller diameter of AgNPs in the range 50–60 nm. A comparison with non-heterocyclic alkyltrimethylphosphonium surfactants of the same alkyl chain length showed better stability and more positive zeta potential values for silver nanodispersions stabilized with heterocyclic phospholium surfactants. Investigations of biological activity of phospholium-capped AgNPs are represented by the studies of antimicrobial activity and cytotoxicity. While cytotoxicity results revealed an increased level of HepG2 cell growth inhibition as compared with the cytotoxicity level of silver-free surfactant solutions, no enhanced antimicrobial action of phospholium-capped AgNPs against microbial pathogens was observed. The comparison of cytotoxicity of AgNPs stabilized with various non-heterocyclic ammonium and phosphonium surfactants shows that AgNPs capped with heterocyclic alkyldimethylphenylphospholium and non-heterocyclic triphenyl-substituted phosphonium surfactants have the highest cytotoxicity among silver nanodispersions stabilized by the series of ammonium and phosphonium surfactants.

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