Dipeptides of S-Substituted Dehydrocysteine as Artzyme Building Blocks: Synthesis,Complexing Abilities and Antiproliferative Properties

Background: Dehydropeptides are analogs of peptides containing at least one conjugate double bond between α,β-carbon atoms. Its presence provides unique structural properties and reaction centre for chemical modification. In this study, the series of new class of dipeptides containing S-substituted dehydrocysteine with variety of heterocyclic moieties was prepared. The compounds were designed as the building blocks for the construction of artificial metalloenzymes (artzymes). Therefore, the complexing properties of representative compounds were also evaluated. Furthermore, the acknowledged biological activity of natural dehydropeptides was the reason to extend the study for antiproliferative action of against several cancer cell lines. Methods: The synthetic strategy involves glycyl and phenylalanyl-(Z)-β-bromodehydroalanine as a substrate in one pot addition/elimination reaction of thiols. After deprotection of N-terminal amino group the compounds with triazole ring were tested as complexones for copper(II) ions using potentiometric titration and spectroscopic techniques (UV-Vis, CD, EPR). Finally, the antiproliferative activity was evaluated by sulforhodamine B assay. Results and Conclusions: A simple and efficient procedure for preparation of dipeptides containing S-substituded dehydrocysteine was provided. The peptides containing triazole appeared to be strong complexones of copper(II) ions. Some of the peptides exhibited promising antiproliferative activities against number of cancer cell lines, including cell lines resistant to widely used anticancer agent.     

Highly Stretchable Conducting SIBS‐P3HT Fibers

Poly(styrene‐β‐isobutylene‐β‐styrene)‐poly(3‐hexylthiophene) (SIBS‐P3HT) conducting composite fibers are successfully produced using a continuous flow approach. Composite fibers are stiffer than SIBS fibers and able to withstand strains of up 975% before breaking. These composite fibers exhibit interesting reversible mechanical and electrical characteristics, which are applied to demonstrate their strain gauging capabilities. This will facilitate their potential applications in strain sensing or elastic electrodes. Here, the fabrication and characterization of highly stretchable electrically conducting SIBS‐P3HT fibers using a solvent/non‐solvent wet‐spinning technique is reported. This fabrication method combines the processability of conducting SIBS‐P3HT blends with wet‐spinning, resulting in fibers that could be easily spun up to several meters long. The resulting composite fiber materials exhibit an increased stiffness (higher Young’s modulus) but lower ductility compared to SIBS fibers. The fibers’ reversible mechanical and electrical characteristics are applied to demonstrate their strain gauging capabilities.     

Characteristics of Polypeptide/Phospholipid Monolayers on Water and the Plasma-Activated Polyetheretherketone Support

Polyetheretherketone (PEEK) is a highly biocompatible polymer widely used in medicine as an implant production material. In this article, the PEEK surface was characterized in terms of its wettabillity properties after the physicochemical modifications by treatment with the low-temperature air plasma and covering with the Langmuir–Blodgett (LB) monolayers of polypeptide (cyclosporine A, CsA) and/or phospholipid (1,2-dipalmitoyl-sn-glycero-3-phosphocholine, DPPC). The LB deposition was preceded by the analysis of miscibility and morphology of monolayers at the air/water interface by means of the Langmuir technique and Brewster angle microscopy (BAM). Then, wettability of the polymer-supported films was evaluated by the contact angle measurements of three probe liquids of different characters (two polar—water and formamide, one apolar—diiodomethane). The measured contact angles allowed for determination of the surface free energy and its components based on the Lifshitz-van der Waals/acid–base (LWAB) approach. Some relations between the kind and magnitude of interactions within the model membranes on the water subphase and those of the PEEK-supported membranes with the liquids were found out. The results allowed obtaining the interesting models of biological coatings with potential applications.     

The Potential of Asiatic Acid in the Reversion of Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats

The purpose of this study was to determine if asiatic acid may act efficiently in the model of cyclophosphamide (CYP)-induced cystitis in rats. We performed experiments after administration of CYP (single dose 200 mg/kg, intraperitoneally), asiatic acid (30 mg/kg/day for 14 consecutive days, by oral gavage), or CYP plus asiatic acid, during which conscious cystometry, measurements of urothelium thickness and bladder edema, as well as selected biomarkers analyses were conducted. In rats that received asiatic acid together with CYP, a drop in bladder basal pressure, detrusor overactivity index, non-voiding contraction amplitude, non-voiding contraction frequency, and the area under the pressure curve were observed, when compared to the CYP group. Furthermore, a significant increase in threshold pressure, voided volume, intercontraction interval, bladder compliance, and volume threshold to elicit NVC were found in that group accordingly. Administration of the asiatic acid successfully restored concentrations of biomarkers both in bladder urothelium (BDNF, CGRP, OCT-3, IL-1β, IL-6, NGF, nitrotyrosine, malondialdehyde, TNF-α, SV2A, SNAP23, SNAP25, PAC-1, ORM1, occludin, IGFBP-3, HB-EGF, T–H protein, Z01, and HPX) and detrusor muscle (Rho kinase and VAChT) in CYP-treated rats. Finally, asiatic acid significantly decreased urothelium thickness and bladder oedema. Asiatic acid proved to be a potent and effective drug in the rat model of CYP-induced cystitis.     

Assessment of cytotoxicity and immune compatibility of phytochemicals‐mediated biosynthesised silver nanoparticles using Cynara scolymus

The study was focused on the phytochemicals‐mediated biosynthesis of silver nanoparticles using leaf extracts and infusions from Cynara scolymus. To identify the antioxidant activity and total phenolic content, the 1,1‐diphenyl‐1‐picrylhydrazyl and Folin–Ciocalteau methods were applied, respectively. The formation and stability of the reduced silver ions were monitored by UV–vis spectrophotometer. The particle sizes of the silver nanoparticles were characterised using the dynamic light scattering technique and scanning electron microscope. The phase composition of the obtained silver nanoparticles was characterised by X‐ray diffraction. The silver nanoparticles suspension, artichoke infusion, and silver ions were separately tested towards potential cytotoxicity and pro‐inflammatory effect using mouse fibroblasts and human monocytes cell line, respectively. The total phenolic content and antioxidant activity of ethanol extract and infusion were found significantly higher as compared to aqueous extract and infusion. The UV–visible spectrophotometric analysis revealed the presence of the characteristic absorption band of the Ag nanoparticles. Moreover, it was found that with the increasing volume of plant extract, the average size of particles was increased. Biocompatibility results evidently showed that silver nanoparticles do not induce monocyte activation, however in order to avoid their cytotoxicity suspension at a concentration <2 ppm should be applied.Inspec keywords: pharmaceuticals, health and safety, renewable materials, toxicology, organic compounds, antibacterial activity, X‐ray diffraction, nanomedicine, nanoparticles, nanofabrication, suspensions, ultraviolet spectra, visible spectra, scanning electron microscopy, silver, particle sizeOther keywords: phytochemicals‐mediated biosynthesis, antioxidant activity, total phenolic content, dynamic light scattering technique, silver nanoparticles suspension, scanning electron microscopy, Cynara scolymus, 1,1 diphenyl‐1‐picrylhydrazyl method, cytotoxicity, immune compatibility, leaf extracts, UV‐vis spectrophotometry, particle size, Folin‐Ciocalteau methods, phase composition, X‐ray diffraction, artichoke infusion, pro‐inflammatory effect, mouse fibroblasts, human monocytes cell line, Ag     

Terahertz time domain spectroscopy of graphene and MXene polymer composites

The rising demand for faster and more efficient electronic devices forces electronics industry to shift toward terahertz frequencies. Therefore there is a growing need for efficient, lightweight, and easy to produce absorbing materials in the terahertz range for electromagnetic interference (EMI) shielding and related applications. This study presents a study on basic optical properties of two types polymer-based composites loaded with two-dimensional structures—graphene and MXene phases (Ti₂C). In said range, total EMI shielding efficiency (SE) and its components, the absorption coefficient (α ), refractive index, and complex dielectric function are investigated. The ratio of SE absorption component to reflection component (SE_ABS :SE_R ) of fabricated composites is equal or higher than 30:1 in over 80% of studied range. The fabricated composites exhibit low (<0.1) loss tangent in studied range. The addition of 1 wt% of graphene increases the composite α over 10-fold in respect to pure polymer–up to 60 cm⁻¹ for frequency higher than 2 THz.     

Antioxidant vs. Prooxidant Properties of the Flavonoid,Kaempferol, in the Presence of Cu(II) Ions: A ROS-Scavenging Activity,Fenton Reaction and DNA Damage Study

Kaempferol is a flavonoid that occurs in tea and in many vegetables and fruits, including broccoli, cabbage, beans, grapes, apples, and strawberries. The efficacy of Kaempferol has been demonstrated in the treatment of breast, esophageal, cervical, ovarian, and liver cancers and leukemia, which very likely arises from its prooxidant properties and the activation of pro-apoptotic pathways. Indeed, this matter has already been the focus of a number of published studies and reviews. The aim of the present study was to elucidate the antioxidant vs. prooxidant properties of flavonoids in the presence of the redox-active metal, copper (II) ion, by means of the Fenton reaction. The specific motivation of this work is that, since an increased level of Cu(II) ions is known to be associated with many disease states such as neurological conditions (Alzheimer’s disease) and cancer, any interaction between these ions and flavonoids might affect the outcome of therapeutic uses of the latter. The structure of the Cu-kaempferol complex in DMSO was investigated by means of low temperature EPR spectroscopy, which confirmed the existence of at least two distinct coordination environments around the copper (II) ion. UV vis-spectra of kaempferol and its Cu(II) complex in DMSO revealed an interaction between the 5-OH (A ring) group and the 4-CO (C ring) group of kaempferol with Cu(II) ions. An ABTS assay confirmed that kaempferol acted as an effective radical scavenger, and that this effect was further enhanced in the form of the Cu(II)-kaempferol complex. Quantitative EPR spin trapping experiments, using DMPO as the spin trap, confirmed suppression of the formation of a mixture of hydroxyl, superoxide, and methyl radicals, in a Fenton reaction system, upon coordination of kaempferol to the redox-active Cu(II) ions, by 80% with respect to the free Cu(II) ions. A viscometric study revealed a better DNA-intercalating ability of the Cu-kaempferol complex than for free kaempferol, essential for conferring anticancer activity of these substances. The results of the viscometric measurements were compared with those from a DNA damage study of Cu-kaempferol complexes in a Fenton reaction system, using gel electrophoresis. At low concentrations of kaempferol (Cu–kaempferol ratios of 1:1 and 1:2), a very weak protective effect on DNA was noted, whereas when kaempferol was present in excess, a significant DNA-protective effect was found. This can be explained if the weakly intercalated kaempferol molecules present at the surface of DNA provide protection against attack by ROS that originate from the Fenton reaction involving intercalated Cu(II)-kaempferol complexes. Following the application of ROS scavengers, L-histidine, DMSO, and SOD, gel electrophoresis confirmed the formation of singlet oxygen, hydroxyl radicals, and superoxide radical anions, respectively. We propose that the prooxidant properties of Cu-kaempferol complexes may provide anticancer activity of these substances. When present in excess, kaempferol displays antioxidant properties under Cu-Fenton conditions. This suggests that kaempferol might prove a suitable candidate for the prevention or treatment of oxidative stress related medical conditions that involve a disturbed metabolism of redox metals such as copper, for example, Menkes disease, and neurological disorders, including Alzheimer’s disease. For the potential use of kaempferol in clinical practice, it will be necessary to optimize the dose size and critical age of the patient so that this flavonoid may be beneficial as a preventive drug against cancer and neurological disorders.