Cytotoxic Potential of a-Azepano- and 3-Amino-3,4-SeCo-Triterpenoids

Semi-synthetic triterpenoids, holding an amino substituted seven-membered A-ring (azepano-ring), which could be synthesized from triterpenic oximes through a Beckmann type rearrangement followed by a reduction of lactame fragment, are considered to be novel promising agents exhibiting anti-microbial, alpha-glucosidase, and butyrylcholinesterase inhibitory activities. In this study, in an attempt to develop new antitumor candidates, a series of A-ring azepano- and 3-amino-3,4-seco-derivatives of betulin, oleanolic, ursolic, and glycyrrhetinic acids were evaluated for their cytotoxic activity against five human cancer cell lines and non-malignant mouse fibroblasts by means of a colorimetric sulforhodamine assay. Azepanoallobetulinic acid amide derivative 11 was the most cytotoxic compound of this series but showed little selectivity between the different human tumor cell lines. Flow cytometry experiments showed compound 11 to act mainly by apoptosis (44.3%) and late apoptosis (21.4%). The compounds were further screened at the National Cancer Institute towards a panel of 60 cancer cell lines. It was found that compounds 3, 4, 7, 8, 9, 11, 15, 16, 19, and 20 showed growth inhibitory (GI₅₀) against the most sensitive cell lines at submicromolar concentrations (0.20–0.94 μM), and their cytotoxic activity (LC₅₀) was also high (1–6 μM). Derivatives 3, 8, 11, 15, and 16 demonstrated a certain selectivity profile at GI₅₀ level from 5.16 to 9.56 towards K-562, CCRF-CEM, HL-60(TB), and RPMI-8226 (Leukemia), HT29 (Colon cancer), and OVCAR-4 (Ovarian cancer) cell lines. Selectivity indexes of azepanoerythrodiol 3 at TGI level ranged from 5.93 (CNS cancer cell lines SF-539, SNB-19 and SNB-75) to 14.89 for HCT-116 (colon cancer) with SI 9.56 at GI₅₀ level for the leukemia cell line K-562. The present study highlighted the importance of A-azepano-ring in the triterpenic core for the development of novel antitumor agents, and a future aim to increase the selectivity profile will thus lie in the area of modifications of azepano-triterpenic acids at their carboxyl group.     

Environmentally Benign Oxidation of Alkylphenols to p-Benzoquinones: A Comparative Study of Various Ti-Containing Catalysts

Catalytic properties of Ti-containing porous solids were compared in the oxidation of 2,3,6-trimethylphenol (TMP) with H₂O₂ to produce 2,3,5-trimethyl-1,4-benzoquinone (TMBQ, vitamin E key intermediate). Mesoporous titanium–silicates with di(oligo)nuclear Ti centers, metal–organic framework MIL-125 and amorphous TiO₂ demonstrated 100 % selectivity toward TMBQ. Titanium–silicates prepared by evaporation-induced self-assembly revealed superior performance in terms of product yield and catalyst reusability.

     

Formic Acid Production Via Methane Peroxide Oxidation Over Oxalic Acid Activated Fe-MFI Catalysts

Topics in Catalysis - The process of synthesis of formic acid via partial peroxide oxidation of methane over Fe-MFI zeolites, as well as the influence of the catalyst activation by oxalic acid on...     

Antimicrobial and Amyloidogenic Activity of Peptides. Can Antimicrobial Peptides Be Used against SARS-CoV-2?

At present, much attention is paid to the use of antimicrobial peptides (AMPs) of natural and artificial origin to combat pathogens. AMPs have several points that determine their biological activity. We analyzed the structural properties of AMPs, as well as described their mechanism of action and impact on pathogenic bacteria and viruses. Recently published data on the development of new AMP drugs based on a combination of molecular design and genetic engineering approaches are presented. In this article, we have focused on information on the amyloidogenic properties of AMP. This review examines AMP development strategies from the perspective of the current high prevalence of antibiotic-resistant bacteria, and the potential prospects and challenges of using AMPs against infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).     

The effect of mechanical recycling on the microstructure and properties of PA66 composites reinforced with carbon fibers

This article aims to prepare by injection molding recycled polymeric composites based on PA66 reinforced with short carbon fibers after artificial aging for applications in the automotive field. The aging cycles involves the combined action of UV radiation, moisture, and temperature in order to simulate the common outdoor conditions. The 100% recycled composites are obtained by the regranulation of the aged specimens followed by the remelting and re‐injection molding. The study is focused on the comparison between the mechanical behavior and the microstructure of the composites before and after mechanical recycling. The results of mechanical, thermal, and morphological investigations reveal that the recycling process had no significant effect on the final properties and microstructure of the recycled composites. Therefore the recycled PA66CF30 composites could be successfully used for structural or semi‐structural automotive applications guaranteeing good final performances and advantages from the environmental point of view. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42275.     

CO adsorption in PdxCoyXz (X = Au,Mo, Ni) tertiary alloy nanocatalysts for PEM fuel cells—a theoretical analysis

Application of tertiary alloy nanoparticles is becoming more important, however, the local structure of such alloyed particles, which is critical for tailoring their properties, is not yet very clearly understood. In this study, we present detailed theoretical analysis on the atomistic structure and CO adsorption in Pd₇₀Co₂₀X₁₀ (X=Au, Mo, Ni) tertiary composite alloys for their application in fuel cells toward oxygen reduction reaction (ORR). Basic structure and the most stable configurations for all the three composites are determined. Quantum mechanical approaches and classic molecular dynamics methods are applied to model the structure and to determine the lowest energy configurations. Our theoretical results agree well with the experimental results of XRD patterns. Considering those structures as the base, simulations were performed to determine the magnitude of CO poisoning. The results obtained by ab‐initio calculations allow us to estimate the CO‐tolerance that these catalysts might have, along with those obtained for Pd‐Co‐Ni (70:20:10 atom %) tertiary alloy, and compared with commercial Pt (1 1 0) catalyst. From these results, a comparison has been made to show different CO adsorption strengths. This is the first step to fabricate an efficient engineering design that allows us to obtain high‐performance, low‐cost nanostructured catalysts. Copyright © 2010 John Wiley & Sons, Ltd.     

Novel A-Ring Chalcone Derivatives of Oleanolic and Ursolic Amides with Anti-Proliferative Effect Mediated through ROS-Triggered Apoptosis

A series of A-ring modified oleanolic and ursolic acid derivatives including C28 amides (3-oxo-C2-nicotinoylidene/furfurylidene, 3β-hydroxy-C2-nicotinoylidene, 3β-nicotinoyloxy-, 2-cyano-3,4-seco-4(23)-ene, indolo-, lactame and azepane) were synthesized and screened for their cytotoxic activity against the NCI-60 cancer cell line panel. The results of the first assay of thirty-two tested compounds showed that eleven derivatives exhibited cytotoxicity against cancer cells, and six of them were selected for complete dose–response studies. A systematic study of local SARs has been carried out by comparative analysis of potency distributions and similarity relationships among the synthesized compounds using network-like similarity graphs. Among the oleanane type triterpenoids, C2-[4-pyridinylidene]-oleanonic C28-morpholinyl amide exhibited sub-micromolar potencies against 15 different tumor cell lines and revealed particular selectivity for non-small cell lung cancer (HOP-92) with a GI₅₀ value of 0.0347 μM. On the other hand, superior results were observed for C2-[3-pyridinylidene]-ursonic N-methyl-piperazinyl amide 29, which exhibited a broad-spectrum inhibition activity with GI₅₀ < 1 μM against 33 tumor cell lines and <2 μM against all 60 cell lines. This compound has been further evaluated for cell cycle analysis to decipher the mechanism of action. The data indicate that compound 29 could exhibit both cytostatic and cytotoxic activity, depending on the cell line evaluated. The cytostatic activity appears to be determined by induction of the cell cycle arrest at the S (MCF-7, SH-SY5Y cells) or G₀/G₁ phases (A549 cells), whereas cytotoxicity of the compound against normal cells is nonspecific and arises from apoptosis without significant alterations in cell cycle distribution (HEK293 cells). Our results suggest that the antiproliferative effect of compound 29 is mediated through ROS-triggered apoptosis that involves mitochondrial membrane potential depolarization and caspase activation.     

Removing of light hydrocarbons from gas mixtures using polymeric composite membranes based on poly(1-trimethylsilylpropyne)

Usually the methodologies used to analyse the feasibility of water reuse projects are focused on the internal costs. The aim of this paper is to show a methodology to assess the feasibility of a water reuse project taking into account not just the internal impact, but also the external impact (environmental and social, for example) and the opportunity cost derived from the project. Internal benefit is obtained from the difference between internal income and internal costs. Internal income is obtained by multiplying the selling price of reclaimed water and the volume obtained. Internal costs are made up of the sum of investment costs, operating costs, financial costs and taxes. While some of these factors identified can be calculated directly in terms of money, biophysical and social aspects demand the definition of units of measurement. In order to homogenize results, an annual reference is proposed. A monetary value can be obtained from the calculation of each impact. However, there are a series of externalities for which no explicit market exists. In these cases economic valuation methods are used, based on hypothetical scenarios or patterns observed in related markets.     

Titanium-monosubstituted polyoxometalates: relation between homogeneous and heterogeneous Ti-single-site-based catalysis

The similarity in the catalytic behaviour of titanium-monosubstituted Keggin type polyoxometalates [PTi(L)W₁₁O₃₉]^n- (Ti-POMs) and heterogeneous titanium single-site catalysts in selective oxidations with H₂O₂ is demonstrated. Recent achievements in the application of Ti-POMs as soluble molecular models for studying mechanisms of oxidation catalysis are reviewed.     

Hemi- and Homozygous Loss-of-Function Mutations in DSG2 (Desmoglein-2) Cause Recessive Arrhythmogenic Cardiomyopathy with an Early Onset

About 50% of patients with arrhythmogenic cardiomyopathy (ACM) carry a pathogenic or likely pathogenic mutation in the desmosomal genes. However, there is a significant number of patients without positive familial anamnesis. Therefore, the molecular reasons for ACM in these patients are frequently unknown and a genetic contribution might be underestimated. Here, we used a next-generation sequencing (NGS) approach and in addition single nucleotide polymor-phism (SNP) arrays for the genetic analysis of two independent index patients without familial medical history. Of note, this genetic strategy revealed a homozygous splice site mutation (DSG2–c.378+1G>T) in the first patient and a nonsense mutation (DSG2–p.L772X) in combination with a large deletion in DSG2 in the second one. In conclusion, a recessive inheritance pattern is likely for both cases, which might contribute to the hidden medical history in both families. This is the first report about these novel loss-of-function mutations in DSG2 that have not been previously identi-fied. Therefore, we suggest performing deep genetic analyses using NGS in combination with SNP arrays also for ACM index patients without obvious familial medical history. In the future, this finding might has relevance for the genetic counseling of similar cases.