Investigation of Leoligin Derivatives as NF-κΒ Inhibitory Agents

The transcription factor NF-κB is an essential mediator of inflammation; thus, the identification of compounds that interfere with the NF-κB signaling pathway is an important topic. The natural products leoligin and 5-methoxyleoligin have served as a starting point for the development of NF-κB inhibitors. Using our modular total synthesis method of leoligin, modifications at two positions were undertaken and the effects of these modifications on the biological activity were investigated. The first modification concerned the ester functionality, where it was found that variations in this position have a significant influence, with bulky esters lacking Michael-acceptor properties being favored. Additionally, the substituents on the aryl group in position 2 of the tetrahydrofuran scaffold can vary to some extent, where it was found that a 3,4-dimethoxy and a 4-fluoro substitution pattern show comparable inhibitory efficiency.

Stimuli-responsive polypeptide nanogels loaded with α1-antitrypsin for inhibition of inflammatory mediator trypsin

A new type of hydrophilic, biocompatible, and biodegradable polypeptide nanogel depots loaded with natural serine protease inhibitor α1-antitrypsin (AAT) was applied for inhibition of inflammatory mediator trypsin. Further, poly[N5-(2-hydroxyethyl)-L-glutamine-ran-N5-propargyl-L-glutamine-ran-N5-(6-aminohexyl)-L-glutamine]-ran-N5-[2-(4-hydroxyphenyl)ethyl)-L-glutamine] (PHEG-Tyr) and Nα-L-Lysine-grafted α,β-poly[(2-propyne)-D,L-aspartamide-ran-(2-hydroxyethyl)-DL-aspartamide-ran-(2-(4-hydroxyphenyl)ethyl)-DL-aspartamide] (Nα-Lys-NG) nanogels were prepared by HRP/H2O2-mediated crosslinking in inverse miniemulsions with pH and temperature-stimuli responsive behavior confirmed by dynamic light scattering and zeta potential measurements. The loading capacity of PHEG-Tyr and Nα-Lys-NG nanogels and their release profiles were firstly optimized with bovine serum albumin (BSA) and then used for loading and release of AAT. PHEG-Tyr and Nα-Lys-NG nanogels showed different loading capacities for AAT with the maximum (20 %) achieved with Nα-Lys-NG nanogel. In both cases, the nanogels depots demonstrated a burst release of AAT during 6 h, which could be favorable for quick inhibition of trypsin. A consequent pilot in vitro inhibition study revealed that both PHEG-Tyr and Nα-Lys-NG nanogels loaded with AAT successfully inhibited the enzymatic activity of trypsin. Furthermore, the inhibitory efficiency of the AAT-loaded nanogels was higher than that of AAT itself, indicating that the negatively charged polypeptide nanogels enhance the inhibitory function of AAT loaded in the nanogel depots.

INHIBITORY EFFICIENCY AND PHYSICOCHEMICAL PROPERTIES OF LIPIDS FROM LEAVES AND JUICE OF ALOE ARBORESCENS Mill.

The composition of lipids isolated from leaves and juice of A. arborescens (7 years ago) and the inhibitory efficiency of lipids from leaves of A. arborescens were studied. The phospholipid (PL) fractions were divided by means of TLC method. The quantitative proportion of PL fractions was determined by spectrophotometrically. The more substantial differences in the composition of PL from leaves and juice of A. arcorescens are revealed in the proportion of the more poorly oxidizable fractions of PL. The more low relative content of PL in the total lipid composition from leaves compared with than in lipids from juice, and shares of sterols are the same for lipids from leaves and juice cause 16% diminution of the molar ratio of [sterols]/[PL] in lipids from juice of A. arborescens. Lipids from leaves are known to characterize the high inhibitory efficiency that is demonstrated by model of the low temperature autoxidation of methyl oleate in the thin layer. Using UV-spectroscopy and the mathematic analysis of spectra by Gauss method the presence of the biologically active substances which contain in lipids was analysed. There are only flavonoids in the chloroform solution of lipids from juice and flavonoids and carotenoids in the small quantity in the chloroform solution of lipids from the leaves of A. arborescens.

Biosynthesis and Characterization of ZnO: Ag2O Nanocomposite for Antifungal Efficacy

In this study, biosynthesis zinc and silver oxide nanocomposite (Bs-ZANc) were prepared using an eco-friendly biological synthesis method using silver nitrate, zinc nitrate hexahydrate, and Lawsonia inermis (Henna) plant extract with four different concentrations; (0.1, 0.2, 0.3, and 0.4) molar. The detailed characterization of Bs-ZANc was performed using Grazing X-ray diffraction technique (G-XRD), Field Emission Scanning Electron Microscope (FE-SEM), X-ray energy dispersive spectroscopy (EDX), Zeta Potential (Z.P.), and Dynamic Light Scattering (DLS). In addition to studying the spectroscopic properties using Fourier transform infrared spectroscopy (FTIR). The result showed good inhibitory efficiency of Bs-ZANc against some types of fungal such as; Penicillium spp., Aspergillus spp., and Candida Albicans. Further, a comparison was made between Bs-ZANc and Lawsonia inermis (Henna) plant extract only regarding antfungal efficacy.

New Hybrid Compounds Combining Fragments of Usnic Acid and Thioether Are Inhibitors of Human Enzymes TDP1, TDP2 and PARP1

Tyrosyl-DNA phosphodiesterase 1 (TDP1) catalyzes the cleavage of the phosphodiester bond between the tyrosine residue of topoisomerase 1 (TOP1) and the 3′ phosphate of DNA in the single-strand break generated by TOP1. TDP1 promotes the cleavage of the stable DNA–TOP1 complexes with the TOP1 inhibitor topotecan, which is a clinically used anticancer drug. This article reports the synthesis and study of usnic acid thioether and sulfoxide derivatives that efficiently suppress TDP1 activity, with IC50 values in the 1.4–25.2 μM range. The structure of the heterocyclic substituent introduced into the dibenzofuran core affects the TDP1 inhibitory efficiency of the compounds. A five-membered heterocyclic fragment was shown to be most pharmacophoric among the others. Sulfoxide derivatives were less cytotoxic than their thioester analogs. We observed an uncompetitive type of inhibition for the four most effective inhibitors of TDP1. The anticancer effect of TOP1 inhibitors can be enhanced by the simultaneous inhibition of PARP1, TDP1, and TDP2. Some of the compounds inhibited not only TDP1 but also TDP2 and/or PARP1, but at significantly higher concentration ranges than TDP1. Leader compound 10a showed promising synergy on HeLa cells in conjunction with the TOP1 inhibitor topotecan.

Mathematical Relationship Based on Experimental Data, for Corrosion Inhibition Mechanism of Phenolic Compounds Obtained from Echium italicum L.

We highlight in this chapter the corrosion protection using phenolic extract. The building of mathematical models using experimental results obtained from the investigation of phenolic molecules or fractions extracted from Echium italicum L., used as corrosion inhibitors is one of the new trends in the study of steel protection. The evaluation of the corrosion inhibition of carbon steel (API 5 L-X60) in a solution 1 M of hydrochloric acid was performed using gravimetric method, potentiodynamic polarization and electrochemical impedance spectroscopy (EIS). The predicted mathematical relationships between the corrosion rate and the inhibitory efficiency in the presence of the butanolic extract of Echium italicum L. (BEEI), when increasing temperature proved a good agreement between experimental and mathematical studies.

Purification and Identification of Cholesterol Micelle Formation Inhibitory Peptides of Hydrolysate from High Hydrostatic Pressure-Assisted Protease Hydrolysis of Fermented Seabass Byproduct

This research focuses on the proteolytic capacity of sea bass byproduct (SB) and their hypocholesterolemic activity via the cholesterol micelle formation (CMF) inhibition. SB was fermented with seven mixed lactic acid bacteria for 5 h at 42 °C. The lactic fermented SB was hydrolyzed with Protease N for 6 h under HHP to obtain the SB hydrolysates (HHP-assisted Protease N hydrolysis after fermentation, F-HHP-PN6). The supernatant was separated from the SB hydrolysate and freeze-dried. As the hydrolysis time extended to 6 h, soluble protein content increased from 187.1 to 565.8 mg/g, and peptide content increased from 112.8 to 421.9 mg/g, while inhibition of CMF increased from 75.0% to 88.4%. Decreasing the CMF inhibitory activity from 88.4% to 42.1% by simulated gastrointestinal digestion (FHHP-PN6 was further hydrolyzed by gastrointestinal enzymes, F-HHP-PN6-PP) reduced the CMF inhibitory activity of F-HHP-PN6. Using gel filtration chromatography, the F-HHP-PN6-PP was fractioned into six fractions. The molecular weight of the fifth fraction from F-HHP-PN6-PP was between 340 and 290 Da, and the highest inhibitory efficiency ratio (IER) on CMF was 238.9%/mg/mL. Further purification and identification of new peptides with CMF inhibitory activity presented the peptide sequences in Ser-Ala-Gln, Pro-Trp, and Val-Gly-Gly-Thr; the IERs were 361.7, 3230.0, and 302.9%/mg/mL, respectively.

RNA-seq analysis of antibacterial mechanism of Cinnamomum camphora essential oil against Escherichia coli

Background Transcriptome analysis plays a central role in elucidating the complexity of gene expression regulation in Escherichia coli. In recent years, the overuse of antibiotics has led to an increase in antimicrobial resistance, which greatly reduces the efficacy of antibacterial drugs and affects people’s health. Therefore, several researchers are focused on finding other materials, which could replace or supplement antibiotic treatment. Methods E. coli was treated with water, acetone and Cinnamomum camphora essential oils, respectively. The antibacterial activity was assessed using the minimum inhibitory concentration (MIC), the minimum bactericidal concentration (MBC), the dry weight and the wet weight of the cells. To explore the antibacterial mechanism of the oil, the RNA-Seq analysis was adopted under three different treatments. Finally, the expression of related genes was verified by Quantitative PCR. Results In this study, we showed that the C. Camphora essential oil exerted a strong antibacterial effect. Our results showed that the inhibitory efficiency increased with increasing of the concentration of essential oil. RNA-seq analysis indicated that the essential oil inhibited the growth of E. coli by inhibiting the metabolism, chemotaxis, and adhesion, meanwhile, life activities were maintained by enhancing E. coli resistance reactions. These results are contributed to uncover the antimicrobial mechanisms of essential oils against E. coli, and the C. Camphora essential oil could be applied as an antibacterial agent to replace or ally with antibiotic.

THE USE OF ONION PEEL EXTRACT TO INHIBIT THE THERMAL OXIDATION OF POLYETHYLENE

The paper studies experimentally the antioxidant activity of onion peel acetone extracts of three varieties (Albion F1, Kaba, Red Baron) in the inhibition process of polyethylene thermal oxidation. The onion varieties differ in the color of their surface scales (colorless (white onion), yellow-orange (yellow onion), red (red onion)) and in the antioxidant properties of their extracts: red onion> yellow onion >> white onion. The results correspond to the mass of the extracted substances. A different sequence of onion varieties has been obtained in terms of the inhibitory effectiveness of their extracts: yellow onion> red onion >> white onion. The comparison of the extracted onion peel extracts with the industrial antioxidant Irganox 1010 in terms of inhibitory efficiency has been carried out. The paper presents and analyzes the IR spectra of the extracts. An increase in the extraction time from 24 hours to 56 days leads to an increase in the antioxidant properties of the extracts of all three varieties, but an increase in the inhibition efficiency is noted only for Albion F1 onion peel extract. In Red Baron and Kaba varieties, the main part of biologically active substances with antioxidant action is extracted from the peel into acetone during the first days of extraction.