Impact of Altitudinal Variation on the Phytochemical Profile,Anthelmintic and Antimicrobial Activity of Two Pinus Species

Active components from natural sources are the current focus in most pharmacological research to provide new therapeutic agents for clinical use. Essential oils from the Pinus species have been traditionally used in medicine. This study aimed to investigate the chemical profile of two Pinus species, Pinus halepensis L. and Pinus pinea Mill, from different altitudes in Libya and study the effect of environmental conditions on the biological activities of essential oils. A clevenger apparatus was used to prepare the essential oils by hydrodistillation. Analyses were done using GC/MS. Anthelmintic and antimicrobial activities were tested against the earthworm Allolobophora caliginosa, gram-positive bacteria, gram-negative bacteria, and fungi. Different chemical profiles were observed among all tested essential oils, and terpenes were the most dominant class. All studied essential oils from the Pinus species exhibited a remarkable anthelmintic activity compared to the standard piperazine citrate drug. Pinus halepensis from both altitudes showed broad-spectrum antimicrobial activity against all tested microorganisms, while Pinus pinea was effective against only Escherichia coli. From these findings, one can conclude that there are variations between studied species. The essential oil compositions are affected by environmental factors, which consequently affect the anthelmintic and antimicrobial activity.     

Crystallography,Molecular Modeling,and COX-2 Inhibition Studies on Indolizine Derivatives

The cyclooxygenase-2 (COX-2) enzyme is an important target for drug discovery and development of novel anti-inflammatory agents. Selective COX-2 inhibitors have the advantage of reduced side-effects, which result from COX-1 inhibition that is usually observed with nonselective COX inhibitors. In this study, the design and synthesis of a new series of 7-methoxy indolizines as bioisostere indomethacin analogues (5a–e) were carried out and evaluated for COX-2 enzyme inhibition. All the compounds showed activity in micromolar ranges, and the compound diethyl 3-(4-cyanobenzoyl)-7-methoxyindolizine-1,2-dicarboxylate (5a) emerged as a promising COX-2 inhibitor with an IC₅₀ of 5.84 µM, as compared to indomethacin (IC₅₀ = 6.84 µM). The molecular modeling study of indolizines indicated that hydrophobic interactions were the major contribution to COX-2 inhibition. The title compound diethyl 3-(4-bromobenzoyl)-7-methoxyindolizine-1,2-dicarboxylate (5c) was subjected for single-crystal X-ray studies, Hirshfeld surface analysis, and energy framework calculations. The X-ray diffraction analysis showed that the molecule (5c) crystallizes in the monoclinic crystal system with space group P 2₁/n with a = 12.0497(6)Å, b = 17.8324(10)Å, c = 19.6052(11)Å, α = 90.000°, β = 100.372(1)°, γ = 90.000°, and V = 4143.8(4)ų. In addition, with the help of Crystal Explorer software program using the B3LYP/6-31G(d, p) basis set, the theoretical calculation of the interaction and graphical representation of energy value was measured in the form of the energy framework in terms of coulombic, dispersion, and total energy.     

Advances in Enzyme and Ionic Liquid Immobilization for Enhanced in MOFs for Biodiesel Production

Biodiesel is a promising candidate for sustainable and renewable energy and extensive research is being conducted worldwide to optimize its production process. The employed catalyst is an important parameter in biodiesel production. Metal–organic frameworks (MOFs), which are a set of highly porous materials comprising coordinated bonds between metals and organic ligands, have recently been proposed as catalysts. MOFs exhibit high tunability, possess high crystallinity and surface area, and their order can vary from the atomic to the microscale level. However, their catalytic sites are confined inside their porous structure, limiting their accessibility for biodiesel production. Modification of MOF structure by immobilizing enzymes or ionic liquids (ILs) could be a solution to this challenge and can lead to better performance and provide catalytic systems with higher activities. This review compiles the recent advances in catalytic transesterification for biodiesel production using enzymes or ILs. The available literature clearly indicates that MOFs are the most suitable immobilization supports, leading to higher biodiesel production without affecting the catalytic activity while increasing the catalyst stability and reusability in several cycles.     

Two‐dimensional separation techniques using supercritical fluid chromatography

High‐resolution separation systems are essential for the analysis of complex mixtures in a wide variety of application areas. To increase resolution, multidimensional chromatographic techniques have been one key solution. Supercritical fluid chromatography provides a unique opportunity in these multidimensional separations based on its potential for high solvent compatibility, rapid duty cycles, and orthogonality to other separation modes. This review focuses on two‐dimensional chromatography methods from the past decade that use supercritical fluid chromatography because of these advantages. Valving schemes and modulation strategies used to interface supercritical fluid chromatography with other liquid chromatography and gas chromatography techniques are described. Particular applications of multidimensional separations using supercritical fluid chromatography for the analysis of oils and chiral separations of pharmaceutical compounds are highlighted. Limitations of and a potential trajectory for supercritical fluid chromatography in this field are also discussed.     

Analysis of Chemical Composition and In Vitro and In Vivo Antifungal Activity of Raphanus raphanistrum Extracts against Fusarium and Pythiaceae,Affecting Apple and Peach Seedlings

The goal of this investigation was to evaluate the in vitro and in vivo efficiency of Raphanus raphanistrum extracts against Fusarium and Pythiaceae species associated with apple and peach seedling decline in Tunisian nurseries. A chemical composition of organic extracts was accomplished using liquid chromatography, thin layer chromatography, and gas chromatography analysis. The in vitro test of three aqueous extract doses of R. raphanistrum against some apple and peach decline agents showed its efficacy in reducing mycelia growth. The in vivo assay of fine powder of this plant on peach seedlings revealed that treatment 8-weeks before the inoculation and planting was more efficient than the treatment before one week. This experiment revealed that the root weight of peach seedlings inoculated by F. oxysporum was improved to 207.29%. For apple seedlings, the treatment 8 weeks before the inoculation and plantation was more efficient than the treatment one week before; it reduced the root browning index. The study of R. raphanistrum chemical composition and its efficiency showed that the glucosinolates products: nitrile (4-Hydroxy-3-(4-methylphenylthio) butane nitrile, benzene acetonitrile, 4-fluoro,butane nitrile, 4-hydroxy-3-[(4-methylphenyl) thio] nitrile), and thiocyanate molecules (thiocyanic acid, ethyle) are responsible for the anti-fungal activities.     

Design,Synthesis, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitory Activity

Scaffolds hybridization is a well-known drug design strategy for antitumor agents. Herein, series of novel indolyl-pyrimidine hybrids were synthesized and evaluated in vitro and in vivo for their antitumor activity. The in vitro antiproliferative activity of all compounds was obtained against MCF-7, HepG2, and HCT-116 cancer cell lines, as well as against WI38 normal cells using the resazurin assay. Compounds 1–4 showed broad spectrum cytotoxic activity against all these cancer cell lines compared to normal cells. Compound 4g showed potent antiproliferative activity against these cell lines (IC₅₀ = 5.1, 5.02, and 6.6 μM, respectively) comparable to the standard treatment (5-FU and erlotinib). In addition, the most promising group of compounds was further evaluated for their in vivo antitumor efficacy against EAC tumor bearing mice. Notably, compound 4g showed the most potent in vivo antitumor activity. The most active compounds were evaluated for their EGFR inhibitory (range 53–79%) activity. Compound 4g was found to be the most active compound against EGFR (IC₅₀ = 0.25 µM) showing equipotency as the reference treatment (erlotinib). Molecular modeling study was performed on compound 4g revealed a proper binding of this compound inside the EGFR active site comparable to erlotinib. The data suggest that compound 4g could be used as a potential anticancer agent.     

A highly selective and sensitive cocaine aptasensor based on covalent attachment of the aptamer-functionalized AuNPs onto nanocomposite as the support platform

Based on the conformational changes of the aptamer-functionalized gold nanoparticles (AuNPs) onto MWCNTs/IL/Chit nanocomposite as the support platform, we have developed a sensitive and selective electrochemical aptasensor for the detection of cocaine. The 5′-amine-3′-AuNP terminated aptamer is covalently attached to a MWCNTs/IL/Chit nanocomposite. The interaction of cocaine with the aptamer functionalized AuNP caused the aptamer to be folded and the AuNPs with negative charge at the end of the aptamer came to the near of electrode surface therefore, the electron transfer between ferricyanide (K₃Fe(CN)₆) as redox probe and electrode surface was inhibited. A decreased current of (K₃Fe(CN)₆) was monitored by differential pulse voltammetry technique. In an optimized condition the calibration curve for cocaine concentration was linear up to 11 μM with detection limit (signal-to-noise ratio of 3) of 100 pM. To test the selectivity of the prepared aptasensor sensing platform applicability, some analgesic drugs as the interferes were examined. The potential of the aptasensor was successfully applied for measuring cocaine concentration in human blood serum. Based on our experiments it can be said that the present method is absolutely beneficial in developing other electrochemical aptasensor.     

A Facile Synthesis of Oxoindenothiazine and Dioxospiro(indene‐2,4′‐thiazine) Derivatives from (Substituted ethylidene)hydrazinecarbothioamides

(E)‐2‐[2‐(1‐Substituted ethylidene)hydrazinyl]‐5‐oxo‐9b‐hydroxy‐5,9b‐dihydroindeno[1,2‐d][1,3]‐thiazine‐4‐carbonitriles and (E)‐5‐oxo‐[(E)‐(1‐substituted ethylidene)hydrazinyl]‐2,5‐dihydroindeno[1,2‐d][1,3]thiazine‐4‐carbonitriles have been obtained from the reaction of 2‐(substituted ethylidene)hydrazinecarbothioamides with 2‐(1,3‐dioxo‐2,3‐dihydro‐1H‐inden‐2‐ylidene)propanedinitrile ( 1 ) in ethyl acetate solution. However, (Z)‐6′‐amino‐1,3‐dioxo‐3′‐substituted‐2′‐[(E)‐(1‐phenylethylidene)hydrazono]‐1,2′,3,3′‐tetrahydrospiro(indene‐2,4′‐[1,3]thiazine)‐5′‐carbonitriles were observed during the reaction of N‐substituted‐2‐(1‐phenylethylidene)hydrazinecarbothioamides with ( 1 ). The structure assignment of products has been confirmed on the basis of ¹H‐, ¹³C‐NMR, and mass spectrometry, as well as theoretical calculations.     

Determination of BTEX in urine samples using cooling/heating-assisted headspace solid-phase microextraction

Excessive and uncontrolled exposures of the workers to benzene, toluene, ethylbenzene and xylene (BTEX) have currently raised great concerns among industrial hygienist all over the world. Therefore, the effective monitoring of such exposures is assumed to be of prime importance. A cold fiber solid-phase microextraction device based on a cooling capsule as a cooling unit and CO₂ as a coolant was applied to quantitatively analyze BTEX in aqueous samples. A gas chromatography with flame ionization detection was recruited to analyze the target analytes, which had been identified according to their retention times. Several factors such as coating temperature, extraction time and temperature, sample volume and sodium content were optimized. Two modes of extraction, i.e., headspace (HS) and headspace cold fiber (HS-CF) in SPME, were investigated and compared under optimized conditions. The results revealed that HS-CF-SPME has the most appropriate outcome for the extraction of BTEX from aqueous samples. Under the optimized conditions, the calibration curves were linear within the range of 0.2–500 ng ml^?1 and the detection limits were between 0.02 and 0.07 ng ml^?1.The intraday relative standard deviations was lower than about 10%. The method was successfully applied to the determination of BTEX in urine samples with good recovery.     

Voltammetric determination of droxidopa in the presence of carbidopa using a nanostructured base electrochemical sensor

A novel carbon paste electrode modified with ZnO nanorods and 2-(4-oxo-3-phenyl-3,4-dihydroquinazolinyl)-N′-phenyl-hydrazinecarbothioamide (2PHCZNCPE) was fabricated and employed to study the electrocatalytic oxidation of droxidopa, using cyclic voltammetry, chronoamperometry and square wave voltammetry as diagnostic techniques. It has been found that the oxidation of droxidopa at the surface of modified electrode occurs at a potential of about 435 mV less positive than that of an unmodified carbon paste electrode. Square wave voltammetry exhibits a linear dynamic range from 7.0 × 10^–8 to 3.0×10^?4 M and a detection limit of 45.0 nM for droxidopa. Finally this modified electrode was used for simultaneous determination of droxidopa and carbidopa.