HPLC Determination of Imidazoles with Variant Anti-Infective Activity in Their Dosage Forms and Human Plasma

A suitable HPLC method has been selected and validated for rapid simultaneous separation and determination of four imidazole anti-infective drugs, secnidazole, omeprazole, albendazole, and fenbendazole, in their final dosage forms, in addition to human plasma within 5 min. The method suitability was derived from the superiority of using the environmentally benign solvent, methanol over acetonitrile as a mobile phase component in respect of safety issues and migration times. Separation of the four anti-infective drugs was performed on a Thermo Scientific^® BDS Hypersil C₈ column (5 µm, 2.50 × 4.60 mm) using a mobile phase consist of MeOH: 0.025 M KH₂PO₄ (70:30, v/v) adjusted to pH 3.20 with ortho-phosphoric acid at room temperature. The flow rate was 1.00 mL/min and maximum absorption was measured with UV detector set at 300 nm. Limits of detection were reported to be 0.41, 0.13, 0.18, and 0.15 µg/mL for secnidazole, omeprazole, albendazole, and fenbendazole, respectively, showing a high degree of the method sensitivity. The method of analysis was validated according to Food and Drug Administration (FDA)guidelines for the determination of the drugs, either in their dosage forms with highly precise recoveries, or clinically in human plasma, especially regarding pharmacokinetic and bioequivalence studies.     

Greenness assessment of a stability indicating simple inexpensive high-performance thin-layer chromatography–dual wavelength method for simultaneous determination of mometasone furoate and salicylic acid in complex matrix using analytical eco-scale

A stability-indicating validated high-performance thin-layer chromatography method was performed for the determination of mometasone furoate (MM) and salicylic acid (SLY), simultaneously within the concentration range of 0.1–1.6 μg/band for MM and 0.4–5 μg/band for SLY. This method was developed to assay the investigated drugs in the presence of their degradation products by alkaline, acidic, neutral, photolytic, and oxidative degradation. Separation was achieved using dual wavelength system, 250 nm for MM and 300 nm for SLY, with mobile phase composed of chloroform–ethanol (9:1, %v/v) and stationary phase of aluminum plates pre-coated with silica gel 60 F₂₄₅. The proposed method is well used for the assay and separation of MM and SLY in pure form and Elicasal^® ointment. The developed method has many advantages such as being rapid, selective and inexpensive. Such advantages promote the suggested method for the high throughput assay of MM and SLY mixture, in pure form and topical preparation. The developed method was validated according to the International Council for Harmonisation guidelines, in terms of linearity, limits of detection and quantification, precision, accuracy, robustness, and specificity. Assessment of greenness has been performed depending on analytical eco-scale approach.

     

Development of Halogenated Pyrazolines as Selective Monoamine Oxidase-B Inhibitors: Deciphering via Molecular Dynamics Approach

Halogens have been reported to play a major role in the inhibition of monoamine oxidase (MAO), relating to diverse cognitive functions of the central nervous system. Pyrazoline/halogenated pyrazolines were investigated for their inhibitory activities against human monoamine oxidase-A and -B. Halogen substitutions on the phenyl ring located at the fifth position of pyrazoline showed potent MAO-B inhibition. Compound 3-(4-ethoxyphenyl)-5-(4-fluorophenyl)-4,5-dihydro-1H-pyrazole (EH7) showed the highest potency against MAO-B with an IC₅₀ value of 0.063 µM. The potencies against MAO-B were increased in the order of –F (in EH7) > –Cl (EH6) > –Br (EH8) > –H (EH1). The residual activities of most compounds for MAO-A were > 50% at 10 µM, except for EH7 and EH8 (IC₅₀ = 8.38 and 4.31 µM, respectively). EH7 showed the highest selectivity index (SI) value of 133.0 for MAO-B, followed by EH6 at > 55.8. EH7 was a reversible and competitive inhibitor of MAO-B in kinetic and reversibility experiments with a Ki value of 0.034 ± 0.0067 µM. The molecular dynamics study documented that EH7 had a good binding affinity and motional movement within the active site with high stability. It was observed by MM-PBSA that the chirality had little effect on the overall binding of EH7 to MAO-B. Thus, EH7 can be employed for the development of lead molecules for the treatment of various neurodegenerative disorders.     

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.