Biological activities of phthalocyanines – XVI. Tetrahydroxy- and tetraalkylhydroxy zinc phthalocyanines. Effect of alkyl chain length on in vitro and in vivo photodynamic activities

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.

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

FEBS Letters ◽

10.1016/s0014-5793(99)01501-x ◽

1999 ◽

Vol 462 (1-2) ◽

pp. 47-50 ◽

Cited By ~ 62

Author(s):

Jürgen Benting ◽

Anton Rietveld ◽

Iris Ansorge ◽

Kai Simons

Keyword(s):

Chain Length ◽

Alkyl Chain ◽

Alkyl Chain Length

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

Journal of Oleo Science ◽

10.5650/jos.ess13154 ◽

2014 ◽

Vol 63 (10) ◽

pp. 995-1004 ◽

Cited By ~ 6

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

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

Bioconjugate Chemistry ◽

10.1021/bc9901144 ◽

2000 ◽

Vol 11 (3) ◽

pp. 306-313 ◽

Cited By ~ 46

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

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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

Antiviral Research ◽

10.1016/s0166-3542(97)00039-9 ◽

1997 ◽

Vol 36 (1) ◽

pp. 43-53 ◽

Cited By ~ 19

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

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

Current Bioactive Compounds ◽

10.2174/1573407216999200422115655 ◽

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.

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Evaluation of the In Vivo Acute Toxicity and In Vitro Hemolytic and Immunomodulatory Activities of the Moringa oleifera Flower Trypsin Inhibitor (MoFTI)

Protein and Peptide Letters ◽

10.2174/0929866527999201113105858 ◽

2020 ◽

Vol 27 ◽

Author(s):

Leydianne Leite de Siqueira Patriota ◽

Dayane Kelly Dias do Nascimento Santos ◽

Bárbara Rafaela da Silva Barros ◽

Lethícia Maria de Souza Aguiar ◽

Yasmym Araújo Silva ◽

...

Keyword(s):

Acute Toxicity ◽

Trypsin Inhibitor ◽

Hemolytic Activity ◽

Moringa Oleifera ◽

Biological Activities ◽

Hematological Parameters ◽

Behavioral Alterations ◽

Female Mice

Background: Protease inhibitors have been isolated from plants and present several biological activities, including immunomod-ulatory action. Objective: This work aimed to evaluate a Moringa oleifera flower trypsin inhibitor (MoFTI) for acute toxicity in mice, hemolytic activity on mice erythrocytes and immunomodulatory effects on mice splenocytes. Methods: The acute toxicity was evaluated using Swiss female mice that received a single dose of the vehicle control or MoFTI (300 mg/kg, i.p.). Behavioral alterations were observed 15–240 min after administration, and survival, weight gain, and water and food consumption were analyzed daily. Organ weights and hematological parameters were analyzed after 14 days. Hemolytic activity of MoFTI was tested using Swiss female mice erythrocytes. Splenocytes obtained from BALB/c mice were cultured in the absence or presence of MoFTI for the evaluation of cell viability and proliferation. Mitochondrial membrane potential (ΔΨm) and reactive oxygen species (ROS) levels were also determined. Furthermore, the culture supernatants were analyzed for the presence of cytokines and nitric oxide (NO). Results: MoFTI did not cause death or any adverse effects on the mice except for abdominal contortions at 15–30 min after administration. MoFTI did not exhibit a significant hemolytic effect. In addition, MoFTI did not induce apoptosis or necrosis in splenocytes and had no effect on cell proliferation. Increases in cytosolic and mitochondrial ROS release, as well as ΔΨm reduction, were observed in MoFTI-treated cells. MoFTI was observed to induce TNF-α, IFN-γ, IL-6, IL-10, and NO release. Conclusion: These results contribute to the ongoing evaluation of the antitumor potential of MoFTI and its effects on other immunological targets.

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Metabolomics of Healthy Berry Fruits

Current Medicinal Chemistry ◽

10.2174/0929867323666161206100006 ◽

2019 ◽

Vol 25 (37) ◽

pp. 4888-4902 ◽

Cited By ~ 3

Author(s):

Gilda D'Urso ◽

Sonia Piacente ◽

Cosimo Pizza ◽

Paola Montoro

Keyword(s):

Biological Activities ◽

Biologically Active ◽

In Vivo Studies ◽

Bioactive Metabolites ◽

Active Metabolites ◽

Positive Effects ◽

Cell Functions ◽

Berry Fruits

The consumption of berry-type fruits has become very popular in recent years because of their positive effects on human health. Berries are in fact widely known for their health-promoting benefits, including prevention of chronic disease, cardiovascular disease and cancer. Berries are a rich source of bioactive metabolites, such as vitamins, minerals, and phenolic compounds, mainly anthocyanins. Numerous in vitro and in vivo studies recognized the health effects of berries and their function as bioactive modulators of various cell functions associated with oxidative stress. Plants have one of the largest metabolome databases, with over 1200 papers on plant metabolomics published only in the last decade. Mass spectrometry (MS) and NMR (Nuclear Magnetic Resonance) are the most important analytical technologies on which the emerging ''omics'' approaches are based. They may provide detection and quantization of thousands of biologically active metabolites from a tissue, working in a ''global'' or ''targeted'' manner, down to ultra-trace levels. In the present review, we highlighted the use of MS and NMR-based strategies and Multivariate Data Analysis for the valorization of berries known for their biological activities, important as food and often used in the preparation of nutraceutical formulations.

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

Current Pharmaceutical Biotechnology ◽

10.2174/1389201020666190318120103 ◽

2019 ◽

Vol 20 (4) ◽

pp. 285-292 ◽

Cited By ~ 5

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.

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Action of Thioglycosides of 1,2,4-Triazoles and Imidazoles on the Oxidative Stress and Glycosidases in Mice with Molecular Docking

Letters in Drug Design & Discovery ◽

10.2174/1573413715666181212150955 ◽

2019 ◽

Vol 16 (6) ◽

pp. 696-710

Author(s):

Mahmoud Balbaa ◽

Doaa Awad ◽

Ahmad Abd Elaal ◽

Shimaa Mahsoub ◽

Mayssaa Moharram ◽

...

Keyword(s):

Oxidative Stress ◽

Molecular Docking ◽

Active Sites ◽

Biological Activities ◽

Imidazole Ring ◽

Quantitative Structure Activity Relationship ◽

Binding Interaction ◽

Qsar Study

Background: ,2,3-Triazoles and imidazoles are important five-membered heterocyclic scaffolds due to their extensive biological activities. These products have been an area of growing interest to many researchers around the world because of their enormous pharmaceutical scope. Methods: The in vivo and in vitro enzyme inhibition of some thioglycosides encompassing 1,2,4- triazole N1, N2, and N3 and/or imidazole moieties N4, N5, and N6. The effect on the antioxidant enzymes (superoxide dismutase, glutathione S-transferase, glutathione peroxidase and catalase) was investigated as well as their effect on α-glucosidase and β-glucuronidase. Molecular docking studies were carried out to investigate the mode of the binding interaction of the compounds with α- glucosidase and β -glucuronidase. In addition, quantitative structure-activity relationship (QSAR) investigation was applied to find out the correlation between toxicity and physicochemical properties. Results: The decrease of the antioxidant status was revealed by the in vivo effect of the tested compounds. Furthermore, the in vivo and in vitro inhibitory effects of the tested compounds were clearly pronounced on α-glucosidase, but not β-glucuronidase. The IC50 and Ki values revealed that the thioglycoside - based 1,2,4-triazole N3 possesses a high inhibitory action. In addition, the in vitro studies demonstrated that the whole tested 1,2,4-triazole are potent inhibitors with a Ki magnitude of 10-6 and exhibited a competitive type inhibition. On the other hand, the thioglycosides - based imidazole ring showed an antioxidant activity and exerted a slight in vivo stimulation of α-glucosidase and β- glucuronidase. Molecular docking proved that the compounds exhibited binding affinity with the active sites of α -glucosidase and β-glucuronidase (docking score ranged from -2.320 to -4.370 kcal/mol). Furthermore, QSAR study revealed that the HBD and RB were found to have an overall significant correlation with the toxicity. Conclusion: These data suggest that the inhibition of α-glucosidase is accompanied by an oxidative stress action.

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