Structural aspects of RimP binding on small ribosomal subunit from Staphylococcus aureus.

Ribosome biogenesis is an energy-intense multistep process where even minimal defects can cause severe phenotypes up to cell death. Ribosome assembly is facilitated by biogenesis factors such as ribosome assembly factors. These proteins facilitate the interaction of ribosomal proteins with rRNA and correct rRNA folding. One of these maturation factors is RimP which is required for efficient 16S rRNA processing and 30S ribosomal subunit assembly. Here, we describe the binding mode of Staphylococcus aureus RimP to the small ribosomal subunit and present a 4.2 Å resolution cryo-EM reconstruction of the 30S-RimP complex. Together with the solution structure of RimP solved by NMR spectroscopy and RimP-uS12 complex analysis by EPR, DEER, and SAXS approaches, we show the specificity of RimP binding to the 30S subunit from S. aureus. We believe the results presented in this work will contribute to the understanding of the RimP role in the ribosome assembly mechanism.

One-Step Synthesis of Functionalized Pyrazolo[3,4-b]pyridines via Ring Opening of the Pyrrolinium Ion.

Herein, we report a highly regioselective one-pot synthesis of pyrazolo[3,4-b]pyridines via the reaction of 3-arylidene-1-pyrrolines with aminopyrazoles. The reaction proceeds through the sequential nucleophilic addition/electrophilic substitution/C-N bond cleavage and provides easy access to pyrazolo[3,4-b]pyridine derivatives featuring a primary amino group. Moreover, the reaction can be terminated at the electrophilic substitution stage, thus providing convenient entry to the hardly accessible pyrazolopyrrolopyridine scaffold.

Silicas with Polyoxyethylene Branches for Modification of Membranes Based on Microporous Block Copolymers.

We have synthesized cubic and linear polysiloxanes containing polyoxyethylene branches (ASiP-Cu) using tetraethoxysilane, polyoxyethylene glycol, and copper chloride as precursors; the products are stable to self-condensation. The effect of copper chloride content on the chemical structure of ASiP-Cu has been established. A special study was aimed at defining the modifying effect of ASiP-Cu on the sorption characteristics of membranes based on microporous, optically transparent block copolymers (OBCs). These OBCs were produced using 2,4-toluene diisocyanate and block copolymers of ethylene and propylene oxides. The study demonstrated significantly increased sorption capacity of the modified polymers. On the basis of the modified microporous block copolymers and 1-(2-pyridylazo)-2-naphthol (PAN) analytical reagent, an analytical test system has been developed. Additionally, the modified OBCs have the benefit of high diffusion permeability for molecules of organic dyes and metal ions. It has been shown that the volume of voids and structural features of their internal cavities contribute to the complex formation reaction involving PAN and copper chloride.

Extent of N-Terminus Folding of Semenogelin 1 Cleavage Product Determines Tendency to Amyloid Formation.

It is known that four peptide fragments of predominant protein in human semen Semenogelin 1 (SEM1) (SEM1(86-107), SEM1(68-107), SEM1(49-107) and SEM1(45-107)) are involved in fertilization and amyloid formation processes. In this work, the structure and dynamic behavior of SEM1(45-107) and SEM1(49-107) peptides and their N-domains were described. According to ThT fluorescence spectroscopy data, it was shown that the amyloid formation of SEM1(45-107) starts immediately after purification, which is not observed for SEM1(49-107). Seeing that the peptide amino acid sequence of SEM1(45-107) differs from SEM1(49-107) only by the presence of four additional amino acid residues in the N domain, these domains of both peptides were obtained via solid-phase synthesis and the difference in their dynamics and structure was investigated. SEM1(45-67) and SEM1(49-67) showed no principal difference in dynamic behavior in water solution. Furthermore, we obtained mostly disordered structures of SEM1(45-67) and SEM1(49-67). However, SEM1(45-67) contains a helix (E58-K60) and helix-like (S49-Q51) fragments. These helical fragments may rearrange into ß-strands during amyloid formation process. Thus, the difference in full-length peptides' (SEM1(45-107) and SEM1(49-107)) amyloid-forming behavior may be explained by the presence of a structured helix at the SEM1(45-107) N-terminus, which contributes to an increased rate of amyloid formation.

Binding of Different Cyclosporin Variants to Micelles Evidenced by NMR and MD Simulations.

Peptides play a critical role in the life of organisms, performing completely different functions. The biological activity of some peptides, such as cyclosporins, can be determined by the degree of membrane permeability. Thus, it becomes important to study how the molecule interacts with lipid bilayers. Cyclosporins C, E, H and L were characterised molecular dynamics simulation; NMR spectroscopy studies were also carried out for cyclosporins C and E. The comparison of one- and two-dimensional spectra revealed certain similarities between spatial structures of the studied cyclosporin variants. Upon dissolving in water containing DPC micelles, which serve as model membranes, subtle changes in the NMR spectra appear, but in a different way for different cyclosporins. In order to understand whether observed changes are related to any structural modifications, simulation of the interaction of the peptide with the phospholipid micelle was performed. The onset of the interaction was observed, when the peptide is trapped to the surface of the micelle. Simulations of this kind are also of interest in the light of the well-known membrane permeability of cyclosporin, which is important for its biological action.

Rare-earth orthovanadate nanoparticles trigger Ca2+-dependent eryptosis.

Introduction. Rare-earth orthovanadate nanoparticles (ReVO4:Eu3+, Re = Gd, Y or La) are promising agents for photodynamic therapy of cancer due to their modifiable redox properties. However, their toxicity limits their application.Objective. The aim of this research was to elucidate pro-eryptotic effects of GdVO4:Eu3+and LaVO4:Eu3+nanoparticles with identification of underlying mechanisms of eryptosis induction and to determine their pharmacological potential in eryptosis-related diseases.Methods. Blood samples (n= 9) were incubated for 24 h with 0-10-20-40-80 mg l-1GdVO4:Eu3+or LaVO4:Eu3+nanoparticles, washed and used to prepare erythrocyte suspensions to analyze the cell membrane scrambling (annexin-V-FITC staining), cell shrinkage (forward scatter signaling), reactive oxygen species (ROS) generation through 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) staining and intracellular Ca2+levels via FLUO4 AM staining by flow cytometry. Internalization of europium-enabled luminescent GdVO4:Eu3+and LaVO4:Eu3+nanoparticles was assessed by confocal laser scanning microscopy.Results.Both nanoparticles triggered eryptosis at concentrations of 80 mg l-1. ROS-mediated mechanisms were not involved in rare-earth orthovanadate nanoparticles-induced eryptosis. Elevated cytosolic Ca2+concentrations were revealed even at subtoxic concentrations of nanoparticles. LaVO4:Eu3+nanoparticles increased intracellular calcium levels in a more pronounced way compared with GdVO4:Eu3+nanoparticles. Our data disclose that the small-sized (15 nm) GdVO4:Eu3+nanoparticles were internalized after a 24 h incubation, while the large-sized (∼30 nm) LaVO4:Eu3+nanoparticles were localized preferentially around erythrocytes.Conclusions.Both internalized GdVO4:Eu3+and non-internalized LaVO4:Eu3+nanoparticles (80 mg l-1) promote eryptosis of erythrocytes after a 24 h exposurein vitrovia Ca2+signaling without involvement of oxidative stress. Eryptosis is a promising model for assessing nanotoxicity.

Antimicrobial activity and cytotoxicity study of cerium oxide nanoparticles with two different sizes.

The control over bacterial diseases requires the development of novel antibacterial agents. The use of antibacterial nanomedicines is one of the strategies to tackle antibiotic resistance. The study was designed to assess the antimicrobial activity of cerium oxide (CeO2 ) nanoparticles (NP) of two different sizes (CeO2 NP1 [1-2 nm] and CeO2 NP2 [10-12 nm]) and their cytotoxicity towards eukaryotic cells. The antimicrobial activity, effects of nanoparticles on DNA cleavage, microbial cell viability, and biofilm formation inhibition were analyzed. The impact of cerium oxide nanoparticles on eryptosis of erythrocytes was estimated using annexin V staining by flow cytometry. The newly synthesized CeO2 NP1 and CeO2 NP2 displayed moderate antimicrobial activities. CeO2 NP1 and CeO2 NP2 exhibited single-strand DNA cleavage ability. CeO2 NPs were found to show 100% microbial cell viability inhibition at a concentration of 500 mg/L. In addition, CeO2 NP1 and CeO2 NP2 inhibited the biofilm formation of S. aureus and P. aeruginosa. Larger cerium oxide nanoparticles were found to be less toxic against erythrocytes compared with the smaller ones. CeO2 nanoparticles demonstrate moderate antimicrobial activity and low cytotoxicity towards erythrocytes, which make them promising antibacterial agents.

CeO2 nanoparticles improve prooxidant/antioxidant balance, life quality and survival of old male rats.

Due to its unique redox chemistry, nanoceria is considered as potent free radical scavenger and antioxidant. However, their protective capacity in aging organisms remains controversial. To detect the anti-aging effects associated with the redox activity of 2 and 10 nm nano-CeO2, different test systems were used, including in vitro analysis, in situ assay of mitochondria function and in vivo studies of suitable nano-CeO2 on aging of male Wistar rats from 22 months-old to the end of life. The 2 nm nanoparticles exhibited not only antioxidant (·OH scavenging; chemiluminescence assay; decomposition of H2O2, phosphatidylcholine autooxidation) but also prooxidant properties (reduced glutathione and reduced nicotinamide adenine dinucleotide phosphate oxidation) as well as affected mitochondria whereas in most test systems 10 nm nano-CeO2 showed less activity or was inert. Prolonged use of the more redox active 2 nm nano-CeO2 (0.25-0.3 mg/kg/day) in vivo with drinking water resulted in improvement in physiological parameters and normalization of the prooxidant/antioxidant balance in liver and blood of aging animals. Survival analysis using Kaplan-Meier curve and Gehan tests with Yates' correction showed that by the time the prooxidant-antioxidant balance was assessed (32 months), survival rates exceeded the control values most considerably. The apparent median survival for the control rats was 900 days, and for the experimental rats-960 days. In general, the data obtained indicate the ability of extra-small 2 nm nano-CeO2 to improve quality of life and increase the survival rate of an aging organism.

Pervaporation Polyurethane Membranes Based on Hyperbranched Organoboron Polyols.

On the basis of aminoethers of boric acid (AEBA), polyurethane vapor-permeable and pervaporative membranes were obtained. AEBAs, the structure of which is modified by bulk adducts (EM) of diphenylol propane diglycidyl ether and ethanolamine, were studied. It turned out that AEBA exists in the form of clusters, and the use of EM as a result of partial destruction of associative interactions leads to a significant decrease in the size of AEBA-EM particles and their viscosity compared to unmodified AEBA. The introduction of EM into the composition of AEBA leads to a threefold increase in the vapor permeability of polyurethanes obtained on their basis. The observed effect is explained by the fact that a decrease in the size of clusters leads to loosening of their dense packing. Areas of clustering due to associative interactions of hydroxyl groups, together with the hydrophilic nature of polyoxyethylene glycol, create channels through which water molecules can penetrate. The increase in vapor permeability is accompanied by a multiple increase in the permeability coefficients in the pervaporative dehydration of isopropanol.

Conformational ensemble of amyloid-forming semenogelin 1 peptide SEM1(68-107) by NMR spectroscopy and MD simulations.

SEM1(68-107) is a peptide corresponding to the region of semenogelin 1 protein from 68 to 107 amino acid position. SEM1(68-107) is an abundant component of semen, which participates in HIV infection enhanced by amyloid fibrils forming. To understand the causes influencing amyloid fibril formation, it is necessary to determine the spatial structure of SEM1(68-107). It was shown that the determination of SEM1(68-107) structure is complicated by the non-informative NMR spectra due to the high intramolecular mobility of peptides. The complementary approach based on the geometric restrictions of individual peptide fragments and molecular modeling was used for the determination of the spatial structure of SEM1(68-107). The N- (SEM1(68-85)) and C-terminuses (SEM1(86-107)) of SEM1(68-107) were chosen as two individual peptide fragments. SEM1(68-85) and SEM1(86-107) structures were established with NMR and circular dichroism CD spectroscopies. These regions were used as geometric restraints for the SEM1(68-107) structure modeling. Even though most of the SEM1(68-107) peptide is unstructured, our detailed analysis revealed the following structured elements: N-terminus (70His-84Gln) forms an α-helix, (86Asp-94Thr) and (101Gly-103Ser) regions fold into 310-helixes. The absence of a SEM1(68-107) rigid conformation leads to instability of these secondary structure regions. The calculated SEM1(68-107) structure is in good agreement with experimental values of hydrodynamic radius and dihedral angles obtained by NMR spectroscopy. This testifies the adequacy of a combined approach based on the use of peptide fragment structures for the molecular modeling formation of full-size peptide spatial structure.

Catalytic Etherification of ortho-Phosphoric Acid for the Synthesis of Polyurethane Ionomer Films.

The etherification reaction of ortho-phosphoric acid (OPA) with polyoxypropylene glycol in the presence of tertiary amines was studied. The reaction conditions promoting the catalytic activity of triethanolamine (TEOA) and triethylamine (TEA) in the low-temperature etherification of OPA were established. The catalytic activity of TEOA and TEA in the etherification reaction of phosphoric acid is explained by the hydrophobic-hydrophilic interactions of TEA with PPG, leading, as a result of collective interactions, to a specific orientation of polyoxypropylene chains around the tertiary amine. When using triethylamine, complete etherification of OPA occurs, accompanied by the formation of branched OPA ethers terminated by hydroxyl groups and even the formation of polyphosphate structures. When triethanolamine is used as a catalyst, incomplete etherification of OPA with polyoxypropylene glycol occurs and as a result, part of the phosphate anions remain unreacted in the composition of the resulting aminoethers of ortho-phosphoric acid (AEPA). In this case, the hydroxyl groups of triethanolamine are completely involved in the OPA etherification reaction, but the catalytic activity of the tertiary amine weakens due to a decrease in its availability in the branched structure of AEPA. The kinetics of the etherification reaction of OPA by polyoxypropylene glycol catalyzed by TEOA and TEA were studied. It was shown that triethanolamine occupies a central position in the AEPA structure. The physico-mechanical and thermomechanical properties of polyurethane ionomer films obtained on the basis of AEPA synthesized in a wide temperature range were studied.

Antimicrobial Effects of Nanostructured Rare-Earth-Based Orthovanadates.

The search for novel antimicrobial agents is of huge importance. Nanomaterials can come to the rescue in this case. The aim of this study was to assess the cytotoxicity and antimicrobial effects of rare-earth-based orthovanadate nanoparticles. The cytotoxicity against host cells and antimicrobial activity of LaVO4:Eu3+ and GdVO4:Eu3+ nanoparticles were analyzed. Effects of nanomaterials on fibroblasts were assessed by MTT, neutral red uptake and scratch assays. The antimicrobial effects were evaluated by the micro-dilution method estimating the minimum inhibitory concentration (MIC) of nanoparticles against various strains of microorganisms, DNA cleavage and biofilm inhibition. GdVO4:Eu3+ nanoparticles were found to be less toxic against eukaryotic cells compared with LaVO4:Eu3+. Both nanoparticles exhibited antimicrobial activity and the highest MIC values were 64 mg/L for E. hirae, E. faecalis and S. aureus shown by GdVO4:Eu3+ nanoparticles. Nanoparticles demonstrated good DNA cleavage activity and induction of double-strand breaks in supercoiled plasmid DNA even at the lowest concentrations used. Both nanoparticles showed the biofilm inhibition activity against S. aureus at 500 mg/L and reduced the microbial cell viability. Taken the results of host toxicity and antimicrobial activity studies, it can be assumed that GdVO4:Eu3+ nanoparticles are more promising antibacterial agents compared with LaVO4:Eu3+ nanoparticles.

Comparison of structural properties of cyclosporin A and its analogue alisporivir and their effects on mitochondrial bioenergetics and membrane behavior.

The paper considers the effect of the MPT pore inhibitor cyclosporin A (CsA) and its non-immunosuppressive analogue alisporivir (Ali) on the functioning of rat skeletal muscle mitochondria. We have shown that both agents at a standard in vitro concentration of 1 µM increase the calcium capacity of organelles and have no effect on the parameters of oxidative phosphorylation. However, an increase in their concentration to 5 µM leads to the suppression of oxygen consumption by mitochondria, which is more pronounced in the case of Ali. This effect is accompanied by a decrease in the membrane potential of organelles and, apparently, is based on the inhibition of electron transport along the mitochondrial respiratory chain due to limited mobility of coenzyme Q. We have noted that both agents do not affect the production of hydrogen peroxide by isolated mitochondria. NMR spectroscopy and molecular dynamics simulation did not reveal significant differences in the structure and backbone flexibility of CsA and Ali. Both agents decrease the overall fluidity of the membrane of DPPC liposomes, inducing an increase in laurdan generalized polarization parameter. A similar effect was also found in the case of mitochondrial membranes. We suggested that these effects of CsA and Ali, associated with their lipophilic nature and the ability to accumulate in the lipid phase of membranes, may cause a decrease in the efficiency of electron transport in the respiratory chain of mitochondria and suppression of the bioenergetics of these organelles.

Design, Spectral Characteristics, Photostability, and Possibilities for Practical Application of BODIPY FL-Labeled Thioterpenoid.

This paper presents the design and a comparative analysis of the structural and solvation factors on the spectral and biological properties of the BODIPY biomarker with a thioterpene fragment. Covalent binding of the thioterpene moiety to the butanoic acid residue of meso-substituted BODIPY was carried out to find out the membranotropic effect of conjugate to erythrocytes, and to assess the possibilities of its practical application in bioimaging. The molecular structure of the conjugate was confirmed via X-ray, UV/vis-, NMR-, and MS-spectra. It was found that dye demonstrates high photostability and high fluorescence quantum yield (to ~100%) at 514-519 nm. In addition, the marker was shown to effectively penetrate the erythrocytes membrane in the absence of erythrotoxicity. The conjugation of BODIPY with thioterpenoid is an excellent way to increase affinity dyes to biostructures, including blood components.

Unraveling the Mechanism of Platelet Aggregation Suppression by Monoterpenoids.

Platelet aggregation causes various diseases and therefore challenges the development of novel antiaggregatory drugs. In this study, we report the possible mechanism of platelet aggregation suppression by newly synthesized myrtenol-derived monoterpenoids carrying different heteroatoms (sulphur, oxygen, or nitrogen). Despite all tested compounds suppressed the platelet aggregation in vitro, the most significant effect was observed for the S-containing compounds. The molecular docking confirmed the putative interaction of all tested compounds with the platelet's P2Y12 receptor suggesting that the anti-aggregation properties of monoterpenoids are implemented by blocking the P2Y12 function. The calculated binding force depended on heteroatom in monoterpenoids and significantly decreased with the exchanging of the sulphur atom with oxygen or nitrogen. On the other hand, in NMR studies on dodecyl phosphocholine (DPC) as a membrane model, only S-containing compound was found to be bound with DPC micelles surface. Meanwhile, no stable complexes between DPC micelles with either O- or N-containing compounds were observed. The binding of S-containing compound with cellular membrane reinforces the mechanical properties of the latter, thereby preventing its destabilization and subsequent clot formation on the phospholipid surface. Taken together, our data demonstrate that S-containing myrtenol-derived monoterpenoid suppresses the platelet aggregation in vitro via both membrane stabilization and blocking the P2Y12 receptor and, thus, appears as a promising agent for hemostasis control.

Toxicity of Nanocomplexes Containing Gadolinium Orthovanadate Nanoparticles and Cholesterol.

Previous studies have shown the ability of nanocomplexes (NCs), which consist of nanoparticles (NPs) of orthovanadates of rare earth metals (GdYVO4:Eu3+) and cholesterol, to inhibit the growth of Ehrlich's ascites carcinoma (EAC). However, the biosafety of these NCs remains unclear. Our objective was to investigate the acute and subchronic toxicity of NCs. NCs were administered to BALB/c mice in NPs concentration of 5.9; 29.5; 59.1; and 118.2 mg/kg. Acute toxicity was induced by a single administration of NCs, subchronic-by repeated daily administration of NCs for 14 days. On day 15 and on day 31 for acute and subchronic toxicity, respectively, the percentage of animal survival, body weight, condition of visceral organs, and activities of γ-glutamyl transferase (GGT) and glucose-6-phosphate dehydrogenase (G-6-PDH) were determined. It was found that administration of NCs in the concentration of 5.9 mg/kg and 29.5 mg/kg of NPs did not influence on survival of animals or have a negative impact on their performance status, morphological and quantitative characteristics of visceral organs, and activities of the GGT and G-6-PDH in the liver. For acute toxicity, the semi-lethal dose (LD50) of nanocomplexes was determined (118.2 mg/kg of NPs). As to subchronic toxicity, it was found that repeated (for 14 days) administration of NCs containing 59.1 mg/kg of NPs decrease survival of animals to 50%. The coefficient of accumulation (Cacum = 7) indicates the low accumulative ability of NCs upon long-term use. Thus, from the LD50 and accumulation coefficient, NCs can be referred to as low-toxic substances and used in conditionally therapeutic doses in oncological practice to develop nanostructured formulations of drugs.

UV Light-Activated GdYVO4:Eu3+ Nanoparticles Induce Reactive Oxygen Species Generation in Leukocytes Without Affecting Erythrocytes In Vitro.

Nanoparticles (NPs) have been reported to be promising enhancement agents for radiation therapy. The aim of the study was to assess the cytotoxicity of UV non-treated and UV pretreated GdYVO4:Eu3+ nanoparticles against erythrocytes and leukocytes by detecting eryptosis and reactive oxygen species (ROS) generation. Levels of intracellular ROS in erythrocytes and leukocytes using a ROS-sensitive dye 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA), as well as eryptosis rate utilizing annexin V staining, following direct exposure to UV-activated and nonactivated NPs were detected by flow cytometry. Blood cells were collected from 9 intact WAG rats. Neither the UV light-untreated GdYVO4:Eu3+ NPs nor the treated ones promoted eryptosis and ROS generation in erythrocytes. Low concentrations of UV light-untreated NPs did not induce oxidative stress in leukocytes, evidenced by unaffected intracellular ROS levels. UV light treatment grants prooxidant properties to NPs, confirmed by NP-induced ROS overproduction in leukocytes. High concentrations of both UV light-treated and untreated NPs altered the redox state of leukocytes. UV light treatment imparts prooxidant properties to GdYVO4:Eu3+ NPs, making them promising radiosensitizing agents in cancer radiation therapy.

Comparative Studies of Orthovanadate Nanoparticles and Metformin on Life Quality and Survival of Senile Wistar Rats.

Effect of prolong use of orthovanadate nanoparticles (GdVO4/Eu3+ NPs (8 × 25 nm)) on life quality and survival of male Wistar rats on the late stage of ontogenesis (from 23 months to the end of life) has been investigated. Multi-parametric assessment of orthovanadate NPs influences against metformin (Met) which is a well-known calorie restriction mimetic (CR-mimetic) has been completed. The quality of life was assessed by taking into account age-related hallmarks-phenotype and some physiological parameters (condition of the coat, body weight, concentration of thyroxine, rectal temperature) as well as indicators of the pro-oxidant/antioxidant balance of blood and liver (the content of lipid hydroperoxides; aconitase, glutathione peroxidase, glutathione reductase, glutaredoxin activity, and activity of NADP+-dehydrogenases (DG) (glucose-6-phosphate DG, malate DG, and isocitrate DG)) in aging animals. Kaplan-Meier curve and Gehan tests with Yates' correction were performed for the survival analysis. It has been found that long-term use of GdVO4/Eu3+ NPs (0.25-0.30 mg/kg/day), as well as Met (100-110 mg/kg/day) with drinking water led to reliable improvement of physiological parameters and normalization of the pro-oxidant/antioxidant balance in the liver and blood of experimental animals. A significant increase in the survival rate of aging rats was observed; the apparent median survival for control rats was 900 days, while for experimental rats, 1010 and 990 days for GdVO4/Eu3+ NPs and Met, respectively. In general, the data obtained demonstrate the ability of GdVO4/Eu3+ NPs and CR-mimetic-Met to improve the quality of life and increase the survival of an elderly organism.

Conjugate of meso-carboxysubstituted-BODIPY with thioterpenoid as an effective fluorescent probe: Synthesis, structure, spectral characteristics, and molecular docking.

This paper is devoted to the design of a fluorescent probe based on meso-carboxysubstituted-BODIPY with a thioterpene fragment. The functional replacement of the methoxy group in the BODIPY molecule on a thioterpene fragment was carried out in order to find out the antiplatelet and anticoagulant action mechanisms of thioterpenoids and to assess the membrane and receptor factors contributions. The molecular structure of the conjugate was confirmed via UV/vis-, NMR- and MS-spectra. It is found that the probe is a high fluorescence quantum yield (to âˆ¼ 100%) in the blue-green region at 509-516 nm. Molecular docking of all studied molecules showed that the BODIPY with terpenoid conjugation is an excellent way to increase their affinity to platelet receptor P2Y12.

Interaction of the pitavastatin with model membranes.

Pitavastatin is a statin drug that, by competitively inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase, can lower serum cholesterol levels of low-density lipoprotein (LDL) accompanied by side effects due to pleiotropic effects leading to statin intolerance. These effects can be explained by the lipophilicity of statins, which creates membrane affinity and causes statin localization in cellular membranes. In the current report, the interaction of pitavastatin with POPC model membranes and its influence on the membrane structure were investigated using H, H and P solid-state NMR spectroscopy. Our experiments show the average localization of pitavastatin at the lipid/water interface of the membrane, which is biased towards the hydrocarbon core in comparison to other statin molecules. The membrane binding of pitavastatin also introduced an isotropic component into the 31P NMR powder spectra, suggesting that some of the lamellar POPC molecules are converted into highly curved structures.