Journal of the Serbian Chemical Society

Simultaneous determination of emtricitabine and tenofovir disoproxil fumarate in pharmaceutical preparations using spectrophotometric, chemometric and chromatographic methods

Aysun Dinçel, E. Damla Gök Topak, Feyyaz Onur — Sun, 21 Apr 2024 00:00:00 +0200

Simple, accurate and sensitive spectrophotometric, chemometric and chromatographic methods were used for the simultaneous determination of emtricitabine (ETC) and tenofovir disoproxil fumarate (TDF) in tablets. In 1^st derivative spectrophotometry, the first derivative spectra of the solution of ETC and TDF in water were recorded as ∆λ = 4 nm and the first derivative absorances were measured at the zero-crossing points at 297.3 and 281.2 nm for ETC and TDF, respectively. In ratio of the 1^st derivative spectrophotometry measurements were recorded at 239.0 and 270.2 nm for ETC and TDF, respectively. Then analytical signals were measured at the wavelengths corresponding to either maximum or minimum for both drugs. For these spectrophotometric methods Beer’s law is obeyed in the concentration range of 2–15 µg mL^-1 for both drugs. As chemometric method, the PLS technique was used. In chromatographic method, the separation was achieved on a C18 column with DAD (262 nm) and isocratic elution of methanol, acetonitrile and 0.1 % orthophosphoric acid in the volume ratio of 40:40:20, respectively, containing the mobile phase. The mean recovery and the relative standard deviation of the methods were found as 97.51–100.17 % and 0.55–1.26 % respectively. All these methods were statistically compared, and they were successfully applied to a pharmaceutical preparation.

Kinetic investigation of reactions of a 3-arylidene-2-thiohydantoin derivative with palladium(II) salts

Petar Stanić, Darko Ašanin, Tanja Soldatović, Marija Živković — Sun, 21 Apr 2024 00:00:00 +0200

¹H-NMR spectroscopy was used to monitor the reactions of an arylidene 2-thiohydantoin derivative, 3-((phenylmethylene)amino)-2-thioxo-4-imidazolidinone (3), with PdCl₂, cis-[PdCl₂(dmso-S)₂] and K₂[PdCl₄] in DMSO-d₆ in order to elucidate the reaction kinetics and mechanism. The 2-thiohydantoin derivative 3 formed cis-[Pd(3-N,S)(dmso-S)₂]⁺ complex (5) in reactions with PdCl₂ and cis-[PdCl₂(dmso-S)₂], while no reaction with K₂[PdCl₄] was observed.
A two-step mechanism for the reactions of 3 with PdCl₂ and cis-[PdCl₂(dmso-S)₂] is proposed, in which fast coordination to the side chain nitrogen occurs in the first step, while chelation and coordination to the sulfur atom in the 2-thiohydantoin ring is the second, slower, rate-determining step. The reaction rate constants were calculated and reactivities of the 2-thiohydantoin derivative 3 towards the palladium(II) salts were compared and discussed. Reaction of 3 with cis-[PdCl₂(dmso-S)₂] was faster than with PdCl2. The investigated palladium(II) salts also react with the solvent, DMSO-d₆, and the influence of these side reactions on the outcome and kinetics of the 2-thiohydantoin derivative complexation reaction is discussed in detail. The obtained results of this study can have an impact in explanation of the coordination behavior of antitumor active palladium(II) and platinum(II) complexes.

Thermoanalytical and spectroscopic studies on medicated jellies with perphenazine

Sun, 21 Apr 2024 00:00:00 +0200

Medicated jellies are widely used by a large part of patients, especially by people with swallowing difficulties. Preformulation studies play an essential role in the development of new pharmaceutical formulations. The present study aimed to formulate and evaluate medicated jellies containing perphenazine, an antipsychotic drug from the group of phenothiazine compounds used to treat schizophrenia and other mental disorders. Typical gelling agents such as sodium alginate (Alg), gelatine (Gel), and pectin (Pec) were used to develop the medicated jellies. In addition to the biopolymers, components such as benzoic acid (BenzAc), citric acid (CitAc), sodium citrate (NaCit), sorbitol (Sorb) and xylitol (Xyl) were also used. Before preparing the jellies, the moist binary mixture between each component of the jelly and the active substance was analysed to investigate the compatibility of the substances. The active substance, moist binary mixture, and medicated jellies were analysed by FTIR_UATR spectroscopy, UV–Vis spectroscopy and thermogravimetry.

Multivariate statistical analysis approach to investigate the thermodynamic quantities of the benign alternative fuel

Sun, 21 Apr 2024 00:00:00 +0200

In order to extract meaningful interpretation from the large data and provide their value to the application areas, chemical data analysis has become a serious challenge in the development and applications of new protocols, technique and methodologies for the mathematical modelling communities and other data science societies. Therefore, in the present work a rapid and robust box-and-whisker plot and multivariate principal component statistical techniques (PCA) are being proposed for the evaluations of the thermodynamic molecular properties data of the benign fuel structures. We observed that, the box-and-whisker plot technique successfully explored all of the thermochemical molecular properties precisely, and described symmetrical distribution of the data along the median values with respect to the rise in temperature. Moreover, applying the PCA technique, the score-plots of PCs diagnosed the peculiar molecular properties variations after a certain peak of temperature with descendant variation in the statistical parameters. Furthermore, PCA parameters not only segregated the thermodynamic properties of propanol and butanol but also, their variations with the temperature. Thus, we concluded that, Box-whisker and PCA statistical techniques are robust and rapid method for the assessment and evaluation of the large molecular thermodynamic quantities data.

A recent tactic for searching CDK-7 kinase inhibitor by NCI database screening

Sun, 21 Apr 2024 00:00:00 +0200

The present study was based on an exploration of NCI database for searching specific CDK-7 kinase inhibitor by HTVS, SP, XP, molecular docking, molecular dynamic simulation, and ADMET evaluation. The best CDK-7 kinase inhibitors (NCI613391, NCI169676, NCI281246, NCI339580) were identified via NCI database screening. The stability of binding interaction between receptor protein and protein-ligand complex of potent finding compounds (NCI613391) was further confirmed by dynamics simulations and MM-GBSA. The RMSD value of receptor and receptor–ligand complexes was analysed, and it revealed the stability of binding interactions and remained stable throughout the simulation. The RMSF values and gyration radius of the unbound receptor and backbone atoms of the complex were found to be equal, which indicates that the drug molecule inside the CDK7 receptor is also stable. The study of MM-GBSA data also revealed stronger binding interactions of ligands to CDK7 receptors. With the exception of NCI169676, all compounds were shown to be substrates for CYP450 2D6, CYP450 3A4, inhibitors of CYP450 2C9, and non-inhibitors of p-glycoprotein. All compounds were qualified and found suitable to be as drug-likeness according to the Lipinski rule, Ghose filter, MDDR like rule and CMC-like rule. The compound (NCI613391) exhibited human intestinal absorption (76.08%), displayed negative AMES and T.E.S.T (US-EPA) toxicity with OSIRIS property and found to be a promising CDK-7 kinase inhibitor and its efficacy may be further explored in clinical trials.

Defluoridation using pinecone-based activated carbon: Adsorption isotherm, kinetics, regeneration and co-ions effect investigation

Parimal Chandra Bhomick, Aola Supong, Akito I. Sema, Dipak Sinha — Sun, 21 Apr 2024 00:00:00 +0200

In this work, cheap and locally available pinecones of Pinus kiseya were used as a precursor to prepare activated carbon using single-step KOH activation for the removal of fluoride from water. The prepared activated carbon’s BET surface area, and total pore volume, were determined as 972.13 m² g^-1 and 0.469 cm³ g^-1, respectively. Batch adsorption studies were evaluated at different contact times, solution pH, adsorbent dose and concentration to obtain the optimum conditions for maximum adsorption. The adsorption data were fitted with the the isotherm models (Langmuir, Freundlich ad Temkin isotherm model) and the adsorption kinetic models. The experimental data were found to best fit using the Langmuir isotherm which confirmed the formation of a monolayer coverage with a maximum adsorption capacity of 2.845 m² g^-1. The adsorption kinetics was well described by the pseudo-second-order model. A study on the effects of co-existing ions showed that fluoride adsorption capacity was observed to decrease in the order: CO₃^2- > SO₄^2- > NO₃^- > Cl^-. The regeneration studies were investigated to determine the reusability of the spent adsorbent. In summary, these findings demonstrated substantial evidence that the activated carbon can be prepared from P. kiseya cones as an eco-friendly adsorbent for the removal of ions such as fluoride from water.

Cost-effective method of simultaneous removal of copper and phosphate on environmentally friendly nanomaterial

Sun, 21 Apr 2024 00:00:00 +0200

Environmentally friendly and economically viable methods are essential in the selection of materials and techniques for the synthesis of nano-zero-valent iron. Plants, with their high polyphenol content and antioxidant capacity, have found application in eco-friendly synthesis processes. The definitive screening design (DSD) monitored four key process parameters for the concurrent removal of copper and phosphate: copper concentration (ranging from 1 to 9 mg L^-1), phosphate concentration (ranging from 1 to 9 mg L^-1), initial pH values (ranging from 2 to 10), and the dosage of nano-zero-valent iron (ranging from 2 to 16 mL). The analysis results provide valuable insights into the significant individual factors influencing the process, along with the potential for their interactions. The model also proposes process optimization to attain maximum removal efficiency, and subsequent verification confirmed its superiority among the alternatives. Mechanisms such as sorption, reduction, complexation, electrostatic attraction, and ligand exchange play pivotal roles in the effective removal of copper and phosphate using nano-zero-valent iron. In summary, this research yields several benefits: the utilization of environmentally sustainable materials, a substantial reduction in experimental complexity, coupled with the ease of the entire procedure, simultaneous and highly efficient copper and phosphate removal, favorable pH levels and, notably, no requirement for additional treatment.

Co-detection of eugenol and butylated hydroxyltoluene by green and selective hydrodistillation of Heliotropium europaeum L. using ionic liquids as additives

Sun, 21 Apr 2024 00:00:00 +0200

This study is the beginning of the research that focuses on unconventional ionic liquids (ILs) hydrodistillation (HD) extraction of the essential oil of Heliotropium europaeum L. using ILs as additives. Two ILs based on 1-butyl-3-methylimidazolium were used by switching the anions (Cl^- and PF₆^-). The effect of mass percent of the added ILs on its yield and composition was evaluated. Compared to the conventional HD, ILs-HD gives a higher yield of essential oils (0.10–0.36 %). Particularly, with [C₄mim][PF₆], the observation of morphological changes using scanning electron microscopy (SEM) confirmed the effectiveness of the ionic liquid in this distillation process. The GC–MS analysis of essential oils (EOs) revealed the presence of sixty-six compounds in HD, ILs-HD methods. Gas chromatography–mass spectrometry analysis of the EOs revealed the predominance of eugenol (1.70–72.35 %), butylated hydroxytoluene (8.95–65.39 %) and phytol (18.20 %). The new distillation methods of H. europaeum with ILs identifies more compounds (50 compounds in ILs-HD [C₄mim][PF₆]; 22 compounds in ILs-HD ([C₄mim][Cl]) than conventional hydrodistillation (25 compounds in HD). Therefore, the ILs-based hydrodistillation approach is superior in improving the production of EOs. It is important to emphasize that the data presented in this study are not yet available for any of this Algerian Heliotropium species of genus and present the great potential of this medicinal plant as a source of novel bioactive extracts with possible therapeutic uses.

In vitro anticancer studies of a small library of cyclic lipopeptides against the human cervix adenocarcinoma HeLa cells

Sun, 21 Apr 2024 00:00:00 +0200

Various cyclic lipopeptides (CLPs, 23 compounds) were tested for their antitumor potential against human cervix adenocarcinoma HeLa cells. From the fast screening (tested concentrations: 0.01 and 10 µM) compound 10 ((12S,6S,10S,13S)-6-((R)-sec-butyl)-7-(2-(dodecylamino)-2-oxoethyl)-13-isopropyl-82-nitro-2,5,12,15-tetraoxo-4,7,11,14-tetraaza-1(1,2)-pyrrolidina-8(1,4)-benzenacyclopentadecaphane-10-carboxamide) was identified as active against HeLa cell line. The MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and CV (crystal violet) assays revealed at least five times higher cytotoxic potential of 10 (IC₅₀ = 12.3±1.8 µM, MTT; 9.4±1.5 µM; CV) in comparison to control drug natural occurring CLP surfactin (IC₅₀ = 64.9±0.8 µM, MTT; 76.2±1.6 µM; CV). The cell cycle analysis performed by DAPI (4',6-diamidino-2-phenylindole) assay indicated the involvement of apoptosis in HeLa cell death upon treatment with 10, which was confirmed by apoptosis assay (annexin V/PI). Furthermore, during this process caspase activation could be detected (ApoStat assay, immunocytochemistry caspase-3 analysis). The flow cytometry analysis did not display induction of autophagy as a possible death mechanism in HeLa cells upon 10 treatment. The current findings could be used to design more effective CLPs based on 10 structure as potential anticancer agents.

Electrochemical analysis of antioxidant status of biological media in different sampling and storage conditions

Irina Goroncharovskaya, Anatoly Evseev, Aslan Shabanov, Sergey Petrikov — Sun, 21 Apr 2024 00:00:00 +0200

The use of an electrochemical approach for assessment of the oxidative stress severity is a promising direction for point-of-care testing development, which is especially important for critically ill patients. The aim of this study was to determine the influence of different types of blood collection tubes (with clot activator and separating gel, lithium heparin, sodium citrate and K₂EDTA) and storage conditions (at 25, 4 and –23 °C up to 5 days) on the electrochemical analysis of the antioxidant status of blood plasma, assessed by measuring the open circuit potential of platinum electrode (OCP) and antioxidant capacity via cyclic voltammetry method (q). It was obtained that blood collection tubes with lithium heparin and clot activator are the most suitable for the electrochemical analysis of antioxidant status of blood plasma, since they do not affect the results of measurements. Furthermore, data obtained during storage blood plasma samples in different temperature conditions indicate that it is preferable to perform electrochemical analysis in fresh samples.

Errata (printed version only)

Editor — Sun, 21 Apr 2024 00:00:00 +0200