Prenylated Trans-Cinnamic Esters and Ethers against Clinical Fusarium spp.: Repositioning of Natural Compounds in Antimicrobial Discovery

Onychomycosis is a common nail infection mainly caused by species belonging to the F. oxysporum, F. solani, and F. fujikuroi species complexes. The aim of this study was to evaluate the in vitro susceptibility of six representative strains of clinically relevant Fusarium spp. toward a set of natural-occurring hydroxycinnamic acids and their derivatives with the purpose to develop naturally occurring products in order to cope with emerging resistance phenomena. By introducing a prenylated chain at one of the hydroxy groups of trans-cinnamic acids 1–3, ten prenylated derivatives (coded 4–13) were preliminarily investigated in solid Fusarium minimal medium (FMM). Minimal inhibitory concentration (MIC) and lethal dose 50 (LD50) values were then determined in liquid FMM for the most active selected antifungal p-coumaric acid 3,3′-dimethyl allyl ester 13, in comparison with the conventional fungicides terbinafine (TRB) and amphotericin B (AmB), through the quantification of the fungal growth. Significant growth inhibition was observed for prenylated derivatives 4–13, evidencing ester 13 as the most active. This compound presented MIC and LD50 values (62–250 µM and 7.8–125 µM, respectively) comparable to those determined for TRB and AmB in the majority of the tested pathogenic strains. The position and size of the prenylated chain and the presence of a free phenol OH group appear crucial for the antifungal activity. This work represents the first report on the activity of prenylated cinnamic esters and ethers against clinical Fusarium spp. and opens new avenues in the development of alternative antifungal compounds based on a drug repositioning strategy.

Novel allyl-ester-based polymers as flow improvers for waxy crude oil

The deposition of paraffin wax from crude oil at low temperatures due to wax deposition, high pour point, high viscosity, and weak flow capability is among the critical and persisting challenges faced by the petroleum industry. In this study, a new para-decyloxy allyl benzoate (I10) was prepared, polymerized into HI10, and copolymerized with dioctadecyl maleate into MHI10 via the free-radical polymerization method employing azobisisobutyronitrile and toluene as the initiator and solvent, respectively. The prepared monomer was characterized by spectroscopic analyses (Fourier-transform infrared (FT-IR)) and proton nuclear magnetic resonance. Further, the polymers were characterized by FT-IR, and their average molecular weights were determined by gel permeation chromatography. The prepared compounds were taken in different concentrations and then tested as flow improvers of Qarun waxy crude oil using pour point depression and rheological parameters. The results of this test indicated that MHI10 exerted the highest effect on pour point reduction and the rheological parameters (yield value and apparent viscosity). Moreover, an increase in the efficiency of the additives was observed after increasing their concentration from 1000 to 5000 ppm.

Increasing Efficiency of Copper-Molybdenum Ore Flotation using Measurement of Pulp Absorption Capacity

A promising line in development of reagent consumption automatic control systems is applying data on measuring collector concentration in the pulp aqueous phase. For effective using data on the concentration of the nonionic collector – allyl ester of amylxanthogenic acid – in the process of flotation, the studies were carried out and the method for analyzing its residual concentration in the flotation pulp liquid phase was developed. The developed spectral technique for measuring the concentration of amylxanthogenic acid allyl ester in the pulp aqueous phase showed stable results in the temperature range of 10 to 25 °С, pH range of 8.5 to 11.0. This allowed applying the technique to measuring residual concentration of AeroMX- 5140 collector in the operation of bulk sulphide flotation in copper-molybdenum ore beneficiation. The laboratory tests allowed determining connection between the indicators of residual concentration with the main indicators of copper-molybdenum flotation. The studies showed that increasing the residual concentration of the non-ionic collector occurs with increasing its consumption and pH of the pulp aqueous phase. It is shown that significant increase in metal recoveries is observed at similar residual collector concentrations: for copper, in the range of 0.25 to 0.5 mg/l, and for molybdenum and pyrite iron, at the concentrations from 0.25 to 1 mg/l. The possibility of using the nonionic collector residual concentration as the informational indicator of the flotation process has been substantiated. It is proposed to use the ore absorption capacity in relation to the collector applied as an indicator of the ore grade. It is shown that using this indicator reduces relative variance for the dependences of the yields of individual ore types and increases the accuracy of determining the composition of the processed ore as a mixture of typical ore grades. An algorithm for automated control of the consumption of flotation reagents based on the advanced control of the processed ore elemental and mineral composition was developed and tested at Erdenet GOK processing plant, with the calculation of the pulp absorption capacity in relation to the nonionic collector, including the beneficiation process indicators determination using an economically-oriented optimization criterion. The expected economic effect from the reduction of metal losses amounted to USD 145 thous.

Route Exploration and Synthesis of the Reported Pyridone-Based PDI Inhibitor STK076545

The enzyme protein disulfide isomerase (PDI) is essential for the correct folding of proteins and the activation of certain cell surface receptors, and is a promising target for the treatment of cancer and thrombotic conditions. A previous high-throughput screen identified the commercial compound STK076545 as a promising PDI inhibitor. To confirm its activity and support further biological studies, a resynthesis was pursued of the reported b-keto-amide with an N-alkylated pyridone at the a-position. Numerous conventional approaches were complicated by undesired fragmentations or rearrangements. However, a successful 5-step synthetic route was achieved using an aldol reaction with an a-pyridone allyl ester as a key step. An X-ray crystal structure of the final compound confirmed that the reported structure of STK076545 was achieved, however its lack of PDI activity and inconsistent spectral data suggest that the commercial structure was misassigned.

Route Exploration and Synthesis of the Reported Pyridone-Based PDI Inhibitor STK076545

The enzyme protein disulfide isomerase (PDI) is essential for the correct folding of proteins and the activation of certain cell surface receptors, and is a promising target for the treatment of cancer and thrombotic conditions. A previous high-throughput screen identified the commercial compound STK076545 as a promising PDI inhibitor. To confirm its activity and support further biological studies, a resynthesis was pursued of the reported b-keto-amide with an N-alkylated pyridone at the a-position. Numerous conventional approaches were complicated by undesired fragmentations or rearrangements. However, a successful 5-step synthetic route was achieved using an aldol reaction with an a-pyridone allyl ester as a key step. An X-ray crystal structure of the final compound confirmed that the reported structure of STK076545 was achieved, however its lack of PDI activity and inconsistent spectral data suggest that the commercial structure was misassigned.

Route exploration and synthesis of the reported pyridone-based PDI inhibitor STK076545

A 5-step synthesis of a reported PDI inhibitor was developed using an aldol reaction with an allyl ester. Conventional approaches for preparing β-keto amides with a pyridone in the alpha position were complicated by undesired fragmentations or rearrangements.

Enhanced Insulation Performances of Crosslinked Polyethylene Modified by Chemically Grafting Chloroacetic Acid Allyl Ester

Modified crosslinked polyethylene (XLPE) with appreciably enhanced DC electrical insulation properties has been developed by chemical modification of grafting chloroacetic acid allyl ester (CAAE), exploring the trapping mechanism of charge transport inhibition. The bound state traps deriving from grafted molecule are analyzed by first-principles calculations, in combination with the electrical DC conductivity and dielectric breakdown strength experiments to study the underlying mechanism of improving the electrical insulation properties. In contrast to pure XLPE, the XLPE-graft-CAAE represents significantly suppressed space charge accumulation, increased breakdown strength, and reduced conductivity. The substantial deep traps are generated in XLPE-graft-CAAE molecules by polar group of grafted CAAE and accordingly decrease charge mobility and raise charge injection barrier, consequently suppressing space charge accumulation and charge carrier transport. The well agreement of experiments and quantum mechanics calculations suggests a prospective material modification strategy for achieving high-voltage polymer dielectric materials without nanotechnology difficulties as for nanodielectrics.

An Efficient Method for Constructing Cyclic β-Amino Acids Bearing Quaternary Stereocenters

This paper describes an efficient method for constructing cyclic β-amino acids bearing quaternary stereocenters. NaHMDS-promoted asymmetric α-alkylation was employed to obtain the key intermediates with quaternary stereogenic centers, which were subsequently reduced by NaBH4 in 10% methanol in THF, with high yields and high diastereoselectivities. By removing the allyl ester group and the chiral auxiliary, the corresponding cyclic β-amino acid hydrochlorides were finally obtained.