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Search results for: cytotoxic activity
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Development and evaluation of RADA-PDGF2 self-assembling peptide hydrogel for enhanced skin wound healing
PublicationBackground: Wound healing complications affect numerous patients each year, creating significant economic and medical challenges. Currently, available methods are not fully effective in the treatment of chronic or complicated wounds; thus, new methods are constantly sought. Our previous studies showed that a peptide designated as PDGF2 derived from PDGF-BB could be a promising drug candidate for wound treatment and that RADA16-I...
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Muramyl dipeptide-based analogs as potential anticancer compounds: Strategies to improve selectivity, biocompatibility, and efficiency
PublicationAccording to the WHO, cancer is the second leading cause of death in the world. This is an important global problem and a major challenge for researchers who have been trying to find an effective anticancer therapy. A large number of newly discovered compounds do not exert selective cytotoxic activity against tumorigenic cells and have too many side effects. Therefore, research on muramyl dipeptide (MDP) analogs has attracted interest...
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Dual-Activity Fluoroquinolone-Transportan 10 Conjugates offer alternative Leukemia therapy during Hematopoietic Cell Transplantation
PublicationHematopoietic cell transplantation (HCT) is often considered a last resort leukemia treatment, fraught with limited success due to microbial infections, a leading cause of mortality in leukemia patients. To address this critical issue, we explored a novel approach by synthesizing antileukemic agents containing antibacterial substances. This innovative strategy involves conjugating fluoroquinolone antibiotics, such as ciprofloxacin...
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Antitumor DNA-Damaging C-1748 is a New Inhibitor of Autophagy that Triggers Apoptosis in Human Pancreatic Cancer Cell Lines
PublicationDespite the enormous progress that has been made over the past decades in diagnosis, treatment and prevention of many types of tumors, survival rates in pancreatic cancer still remain poor. Pancreatic cancer is one of the most malignant and chemoresistant tumors and the profound mechanism supporting these phenomena is the constitutively activated prosurvival autophagy. The antitumor 1-nitroacridine derivative C-1748 belongs to...
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Targeting of FLT3-ITD kinase contributes to high selectivity of imidazoacridinone C-1311 against FLT3-activated leukemia cells
PublicationDrugs targeting receptor tyrosine kinase FLT3 are of particular interest since activating FLT3-internal tandem duplication (ITD) mutations abundantly occur in fatal acute myeloid leukemias (AMLs). Imidazoacridinone C-1311, a DNA-reactive inhibitor of topoisomerase II, has been previously shown to be a potent and selective inhibitor of recombinant FLT3. Here, we expand those findings by studying its effect on leukemia cells with...
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Fluorescent analogs of trypsin inhibitor SFTI-1 isolated from sunflower seeds-synthesis and applications
PublicationThis article describes the synthesis and enzymatic study of newly synthesized analogs of trypsin inhibitors SFTI-1 that were fluorescent labeled on their N-terminal amino groups. Two fluorescent derivatives of benzoxazole (3-[2-(4-diphenylaminophenyl) benzoxazol-5-yl]-L-alanine[(4NPh(2)) Ph] Box-Ala and 3-[2-(2', 4', 5'-trimethoxyphenyl) benzoxazol-5-yl]-l-alanine-[2,4,5-(OMe)3Ph] Box-Ala) were used as efficient fluorescent labels....
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In Vitro and In Vivo Imaging-Based Evaluation of Doxorubicin Anticancer Treatment in Combination with the Herbal Medicine Black Cohosh
PublicationAs a substitution for hormone replacement therapy, many breast cancer patients use black cohosh (BC) extracts in combination with doxorubicin (DOX)-based chemotherapy. In this study, we evaluated the viability and survival of BC- and DOX-treated MCF-7 cells. A preclinical model of MCF-7 xenografts was used to determine the influence of BC and DOX administration on tumor growth and metabolism. The number of apoptotic cells after...
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Distinct cellular uptake patterns of two anticancer unsymmetrical bisacridines and their metabolic transformation in tumor cells.
PublicationUnsymmetrical bisacridines (UAs) represent a novel class of anticancer agents. Their high cytotoxicity towards multiple human cancer cell lines and inhibition of human tumor xenograft growth in nude mice signal their potential for cancer treatment. Therefore, the mechanism of their strong biological activity is broadly investigated. Here, we explore the efflux and metabolism of UAs, as both strongly contribute to the development...
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New Unsymmetrical Bisacridine Derivatives Noncovalently Attached to Quaternary Quantum Dots Improve Cancer Therapy by Enhancing Cytotoxicity toward Cancer Cells and Protecting Normal Cells
PublicationThe use of nanoparticles for the controlled drug delivery to cells has emerged as a good alternative to traditional systemic delivery. Quantum dots (QDs) offer potentially invaluable societal benefits such as drug targeting and in vivo biomedical imaging. In contrast, QDs may also pose risks to human health and the environment under certain conditions. Here, we demonstrated that unique combination of nanocrystals core components...
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Synthesis and Biological Evaluation of Acridine/Acridone Analogs as Potential Anticancer Agents
PublicationAcridine and acridone analogues were prepared by Ullmann condensation and then cyclization reaction. As a result of nucleophilic substitution reaction 1-nitro-9-phenoxyacridine or 1-chloro-4-nitro-9(10H)-acridone with the corresponding peptides, the planned acridine derivatives (10a-c, 12, 17-a-d, 19) have been obtained. The cytotoxic activity of the newly obtained analogs were evaluated against melanotic (Ma) and amelanotic (Ab)...
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Anticancer Study on IrIII and RhIII Half-Sandwich Complexes with the Bipyridylsulfonamide Ligand
PublicationTwo non-platinum compounds, organometallic half-sandwich complexes [(η 5 -Cp)IrCl(L)]PF 6 (1) and [(η 5 -Cp)RhCl(L)]PF 6 (2) were prepared by treating pentamethylcyclopentadienyl chloride dimers of iridium(III) or rhodium(III) with the obtained 4-amino-N-(2,2'-bipyridin-5- yl)benzenesulfonamide ligand (L) and ammonium hexafluorophosphate. The crystal structures of ligand (L) and complexes 1 and 2 were obtained and then analyzed. Coordination...
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Quantum dots conjugates with unsymmetrical bisacridines enhance cytotoxicity of these antitumor compounds in lung cancer cells and have protecting effects on normal cells
PublicationBackground: In recent years, with the rapid development of nanotechnology and its extensive applications in the medicine, nanocarriers for anticancer drug delivery have gained a great importance. Spherical semiconductor nanocrystals, frequently called quantum dots (QDs) are very attractive nanomaterials for bioimaging applications and they possess properties as potential candidates for drug carrier. Unsymmetrical bisacridines (UAs),...
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The Action Mechanisms, Anti-Cancer and Antibiotic-Modulation Potential of Vaccinium myrtillus L. Extract
PublicationHerbal medicinal products containing Vaccinium myrtillus L. (bilberry) fruits and fruit extracts are widely available in the market. Although bilberry leaves and stems are considered as bio-waste, they contain much higher levels of phenolic compounds than fruits. The study aimed to investigate the antimicrobial and anticancer potential of aerial part extracts from Vaccinium myrtillus L. (V. myrtillus, VM) plants harvested at high...
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Induction of G2/M phase arrest and apoptosis of human pancreatic cancer BxPC-3 cells by potenet antitumor 1-nitroacridine derivative C-1748
PublicationPancreatic ductal adenocarcinoma (PDA) is among the most lethal human cancers, in part because it is insensitive to many chemotherapeutic drugs. Gemcitabine still remains the best chemotherapeutic agent available for the treatment of advanced pancreatic cancer. However, gemcitabine treatment results in only a marginal survival advantage. Thus, there is a strong need for the continuous development of novel therapeutic agents...
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Antitumor 1-nitroacridine derivative C-1748 induces significant apoptosis in pancreatic cancer cells.
PublicationPancreatic cancer is the fifth leading cause of cancer death and has the lowest survival rate of any solid cancer in the industrial countries. The poor prognosis of pancreatic cancer results from its tendency for late presentation, aggressive invasion, early metastasis, and resistance to chemotherapy. Gemcitabine still remains the best chemotherapeutic agent available for the treatment of advanced pancreatic cancer. However, gemcitabine...
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Growth inhibition of cultured cancer cells by Ribes nigrum leaf extract
PublicationThe present article includes data on the possible selective cytotoxic effect of extract of Ribes nigrum L. growing at high Armenian landscape. For this purpose, different non-cancer (microglial BV-2 wild type (Wt), acyl-CoA oxidase 1 (ACOX1) deficient (Acox1-/-) and cancer (human colon adenocarcinoma HT29 and human breast cancer MCF7) cell lines were applied. R. nigrum leaf ethanol extract showed a growth inhibition effect towards...
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Electrochemical simulation of enzymatic transformations studied for the selected antitumor acridine derivatives
PublicationThe elucidation of the metabolic pathways and the biotransformation mechanisms of potential drugs is a crucial point in drug development. It allows to know the activation routes of the new biologically active compounds, especially in respect to their possible toxicity. Generally, in vivo or in vitro experiments with liver microsomes or hepatocytes are performed. However, these testing schemes are tedious, time consuming and of...
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Electrochemistry meets enzymes: Investigation of the biotransformation pathway of C-1311 based on electrochemical simulation in comparison to in vitro methods.
PublicationThe knowledge of the metabolic pathways and the biotransformation of new drugs is one of the major challenges in pharmaceutical research. It is crucial for elucidation of degradation routes of the new biologically active compounds, especially in the area of possible toxicity. Conventional in vitro drug metabolism studies are based on incubating drug candidate with e.g. hepatocytes or, most importantly, liver cell microsomes and...
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Surface-dependent biological potential of spherical silver nanoparticles
Open Research DataThe growing interest in silver nanoparticles (AgNPs) is largely driven by their significant antimicrobial potential. As carriers of reactive silver ions on a nanoscale, AgNPs are considered excellent candidates for specific antibacterial strategies. Numerous scientific studies have highlighted that AgNPs are broad-spectrum antimicrobials, with their...
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Biocompatibility and potential functionality of lanthanum-substituted cobalt ferrite spinels
PublicationBulk and nanostructurized lanthanum-cobalt spinels have attracted a lot of interest from researchers, due to their unique physical and chemical properties as well as functionalities, which are interesting for biomedical and electronic industries. In this manuscript we show that introducing small lanthanum (La3+) content can tune magnetic, electronic and cytotoxic properties of the CoFe2− xLaxO4 system (x ≤ 0.1). The mechanisms...
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Obtaining and Characterization of the PLA/Chitosan Foams with Antimicrobial Properties Achieved by the Emulsification Combined with the Dissolution of Chitosan by CO2 Saturation
PublicationA new method of obtaining functional foam material has been proposed. The materials were created by mixing the poly lactic acid (PLA) solution in chloroform, chitosan (CS) dissolved in water saturated with CO2 and polyethylene glycol (PEG), and freeze-dried for removal of the solvents. The composite foams were characterized for their structural (SEM, FT-IR, density, porosity), thermal (DSC), functional (hardness, elasticity, swelling...
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Obtaining and Characterization of the PLA/Chitosan Foams with Antimicrobial Properties Achieved by the Emulsification Combined with the Dissolution of Chitosan by CO2 Saturation
PublicationA new method of obtaining functional foam material has been proposed. The materials were created by mixing the poly lactic acid (PLA) solution in chloroform, chitosan (CS) dissolved in water saturated with CO2 and polyethylene glycol (PEG), and freeze-dried for removal of the solvents. The composite foams were characterized for their structural (SEM, FT-IR, density, porosity), thermal (DSC), functional (hardness, elasticity, swelling...
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Influence of silver nanoparticles addition on antibacterial properties of PEO coatings formed on magnesium
PublicationMagnesium is a biodegradable material and thus could be a choice for bone fixation devices and implants with a specific purpose. This study aims to enhance the anti-corrosive, biocompatible, and antibacterial properties on magnesium-based materials through ceramic coatings formation. To achieve this the silicate-based electrolyte was used to create of Plasma Electrolytic Oxidation (PEO) coatings. During investigation the bioactive...
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Progress in targeting tumor cells by using drug-magnetic nanoparticles conjugate.
PublicationTo limit the cytotoxicity of anticancer drugs against healthy cells, an appropriate carrier should be synthesized to deliver the drug to the tumor tissue only. A good solution is to anchor a magnetic nanoparticle to the molecule of the drug and to use a properly directed external magnetic field. We have shown that the improved by us synthesis of the conjugate of doxorubicin with iron-oxide magnetic nanoparticles allows a substantial...
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Modified Peptide Molecules As Potential Modulators of Shelterin Protein Functions; TRF1
PublicationIn this work, we present studies on relatively new and still not well-explored potential anticancer targets which are shelterin proteins, in particular the TRF1 protein can be blocked by in silico designed "peptidomimetic" molecules. TRF1 interacts directly with the TIN2 protein, and this protein-protein interaction is crucial for the proper functioning of telomere, which could be blocked by our novel modified peptide molecules....
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The relationship between phytochemical composition and biological activities of differently pigmented varieties of berry fruits; Comparison between embedded in food matrix and isolated anthocyanins.
PublicationThe aim of this research was to correlate the composition of phenolic compounds and bioactivities (antioxidant, cytotoxic, antigenotoxic, and influence on selected enzymatic activities) exhibited by extracts from differently pigmented raspberry (yellow and red), grape (white and red), mulberry (white and black), and currant (white, red, and black) varieties. It was presumed that phytocomplexes of the same species will be similar...
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Improved cytotoxicity and preserved level of cell death induced in colon cancer cells by doxorubicin after its conjugation with iron-oxide magnetic nanoparticles
PublicationA promising strategy for overcoming the problem of limited efficacy in antitumor drug delivery and in drug release is the use of a nanoparticle-conjugated drug. Doxorubicin (Dox) anticancer chemotherapeutics has been widely studied in this respect, because of severe cardiotoxic side effects. Here, we investigated the cytotoxic effects, the uptake process, the changes in cell cycle progression and the cell death processes in the...
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Imidazoacridinone-dependent lysosomal photodestruction: a pharmacological Trojan horse approach to eradicate multidrug-resistant cancers
PublicationMultidrug resistance (MDR) remains a primary hindrance to curative cancer therapy. Thus, introduction of novel strategies to overcome MDR is of paramount therapeutic significance. Sequestration of chemotherapeutics in lysosomes is an established mechanism of drug resistance. Here, we show that MDR cells display a marked increase in lysosome number. We further demonstrate that imidazoacridinones (IAs), which are cytotoxic fluorochromes,...
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Novel anticancer strategy aimed at targeting shelterin complexes by the induction of structural changes in telomeric DNA: hitting two birds with one stone.
PublicationThe ends of chromosomes in mammals are composed of telomeric DNA containing TTAGGG repeats, which bind specific proteins called shelterins. This telomeric DNA together with shelterins form a cap that protects the ends of chromosomes from being recognized as sites of DNA damage and from chromosomal fusions. Many very successful antitumor drugs used in the treatment of cancer patients bind to DNA, some of them with a prominent sequence...
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CHEMOTHERAPY-MEDIATED COMPLICATIONS OF WOUND HEALING. AN UNDERSTUDIED SIDE EFFECT
PublicationSignificance: Chemotherapy is a primary method to treat cancer, but while cytotoxic drugs are designed to target rapidly dividing cancer cells, they can also affect other cell types, including dermal cells and macrophages involved in wound healing, which often leads to the development of chronic wounds. The situation becomes even more severe when chemotherapy is combined with surgical tumor excision. Recent advances: Despite its...
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Impact of Brake Wear Particles on Eukaryotic Cell Viability and Associated Oxidative Stress Responses
PublicationIn this study, the cytotoxic effects of brake wear particles (≥250 nm ceramic/ceramic wear particles (CCWPs) and ≤100 nm ceramic/steel wear particles (CSWPs)) and 100 nm iron (III) oxide ultrafine particles (IOUFPs) on human lung carcinoma (A549) and Chinese hamster ovary (CHO) cells were investigated. Cell viability was determined using the MTT and Calcein AM methods. Oxidative stress was assessed by measuring reactive oxygen...
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A vector-enzymatic DNA fragment amplification-expression technology for construction of artificial, concatemeric DNA, RNA and proteins for novel biomaterials, biomedical and industrial applications
PublicationA DNA fragment amplification/expression technology for the production of new generation biomaterials for scientific, industrial and biomedical applications is described. The technology enables the formation of artificial Open Reading Frames (ORFs) encoding concatemeric RNAs and proteins. It recruits the Type IIS SapI restriction endonuclease (REase) for an assembling of DNA fragments in an ordered head-to-tail-orientation. The...
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Functionalized Peptide Fibrils as a Scaffold for Active Substances in Wound Healing
PublicationTechnological developments in the field of biologically active peptide applications in medicine have increased the need for new methods for peptide delivery. The disadvantage of peptides as drugs is their low biological stability. Recently, great attention has been paid to self-assembling peptides that can form fibrils. Such a formulation makes bioactive peptides more resistant to enzymatic degradation and druggable. Peptide fibrils...
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Human UDP-Glucuronosyltransferases: Effects of altered expression in breast and pancreatic cancer cell lines.
PublicationIncreased aerobic glycolysis and de novo lipid biosynthesis are common characteristics of invasive cancers. UDP-glucuronosyltransferases (UGTs) are phase II drug metabolizing enzymes that in normal cells possess the ability to glucuronidate these lipids and speed their excretion; however, de-regulation of these enzymes in cancer cells can lead to an accumulation of bioactive lipids, which further fuels cancer progression. We hypothesize...
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Anti-cancer effect of Rumex obtusifolius in combination with arginase/nitric oxide synthase inhibitors via downregulation of oxidative stress, inflammation, and polyamine synthesis
PublicationCancer continues to be a leading cause of death worldwide, making the development of new treatment methods crucial in the fight against it. With cancer incidence rates increasing worldwide, ongoing research must focus on identifying new and effective ways to prevent and treat the disease. The combination of herbal extracts with chemotherapeutic agents has gained much interest as a novel strategy to combat cancer. Rumex obtusifolius...
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Copper(II) complexes with substituted imidazole and chlorido ligands: X-ray, UV-Vis, magnetic and EPR studies and chemotherapeutic potential
PublicationCrystal structures, UV-Vis and EPR spectra and magnetic properties of four copper(II) complexes with chloride anions and 4-methylimidazole, 2-ethylimidazole, 2-isopropylimidazole or 2-ethyl-4-methylimidazole are described. In the solid state three of the complexes are mononuclear and one complex with 2-ethylimidazole is binuclear with bridging chlorido ions. UV-Vis spectra of the methanolic solutions of the complexes show LMCT...
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Reactions of cobalt(ii) chloride and cobalt(ii) acetate with hemisalen-type ligands: ligand transformation, oxidation of cobalt and complex formation. Preliminary study on the cytotoxicity of Co(ii) and Co(iii) hemisalen complexes
PublicationSeveral molecular cobalt(II) complexes, one Co(II) coordination polymer, and one ionic cobalt(III) complex with imine hemisalen ligands were synthesized. The hemisalen ligands were synthesized from o-vanillin (oVP) and diverse aminopyridines (compounds HL1–HL4) or aminophenol (compound HL5). It was observed that cobalt(II) chloride in dry acetonitrile catalyzes a transformation of HL1 and HL3 instead of complex formation. The conversion...