Comparative study of experimental and DFT calculations for 3-cinnamoyl 4-hydroxycoumarin derivatives.

BACKGROUND: Computational research plays an important role in predicting the chemical and physical properties of biologically active compounds important in future structural modifications to improve or modify biological activity. OBJECTIVE: This research focuses on quantum chemical and spectroscopic investigations properties of synthesized 4-hydroxycoumarin derivatives. METHODS: Quantum chemical calculations were obtained using B3LYP, HF, and M06-2x level methods with the 6-31++G (d,p) basis set. Afterward, IR, 1H, 13C, UV-Visible experimentally parameters were compared with the results obtained using the B3LYP/6-31+G*(d) basis set of the molecules to be able to characterize the structures. RESULTS: Based on the quantum chemical calculations compound with acetamido group on the phenyl ring is the most reactive, and compound with nitro substituent is the least reactive and the the strongest electrophile among tested compounds. With the exception of compounds with dimethylamino group, all other compounds have a pronounced tautomer between OH and C = O group. The calculated and experimental values are in agreement with each other. CONCLUSION: The molecular structure in the ground state of six 3-cinnamoyl 4-hydroxycoumarin derivatives was optimized using density functional theory. The observed and computed values were compared and it can be concluded that the theoretical results were in good linear agreement with the experimental data.

HPLC method for the determination of thymoquinone in growth cell medium.

BACKGROUND: Preclinical drug testing requires in vitro and in vivo assessments that are vital for studying drug pharmacokinetics and toxicity. Distinct factors that play an important role in drug screening, such as hydrophobicity, solubility of the substance and serum protein binding can be challenging by inducing result inconsistencies. Hence, establishing accurate methods to quantify drug concentrations in cell cultures becomes pivotal for reliable and reproducible results important for in vivo dosing predictions. OBJECTIVE: This research focuses on developing an optimized analytical approach via high-pressure liquid chromatography (HPLC) to determine thymoquinone (TQ) levels in monolayer cell cultures. METHODS: The method's validation adheres to the International Council for Harmonisation (ICH) guideline M10, ensuring its acceptance and applicability. Using an HPLC system with a Diode Array Detector (DAD), the study fine-tuned various parameters to achieve an efficient separation of TQ. Validation covered specificity, sensitivity, matrix effects, linearity, precision, and accuracy, alongside assessing TQ stability in RPMI-1640 medium. RESULTS: The HPLC method exhibited remarkable TQ specificity, free from interfering peaks at the analyte retention. Sensitivity analysis at the lower limit of quantification (LLOQ) revealed 5.68% %CV and 98.37% % mean accuracy. Matrix effect evaluation showcased accuracy within 85-115%. Linearity spanned in the concentration range of 2-10 µM with a correlation coefficient (r2) of 0.9993. Precision and accuracy were aligned with acceptance criteria. The proposed method was found to be greener in terms of usage of persistent, bioaccumulative, and toxic chemicals and solvents, corrosive samples, and waste production. CONCLUSION: The developed HPLC-DAD method emerges as specific, accurate, sensitive, and reliable for TQ determination in cell cultures. It ensures robust TQ quantification, enhancing precise in vitro assessments and dependable dosing predictions for in vivo studies. Further research is advocated to investigate TQ's stability across diverse environmental conditions.

Anti - proliferative and anti - inflammatory activity of triterpene extracts from plant species belonging to Lamiaceae family / Actividad antiproliferativa y antinflamatoria de los extractos de triterpenos de plantas pertenecientes a la familia Lamiaceae

Triterpenes are very important secondary metabolites with wide structural diversity and significant role in pharmacy and medicine. In the present research, a comparative study of pharamacological activities of the triterpene fractions obtained from several plant species belonging to Lamiaceae family, was carried out. In - vitro anti - proliferative activity was performed using a standard proliferation assay based on tetrazolium salts. In vitro anti - inflammatory activity of triterpene fractions was determined by an assay of inhibition of albumin denaturation. In general, the triterpene fractions obtained from plant species belonging to Lam iaceae family showed a strong anti - proliferative activity and anti - inflammatory activity. The triterpene fraction of Rosmarini folium showed the strongest anti - proliferative activity (GI 50 range from 4 to 37 µg/ml) and the strongest anti - inflammatory activ ity in the range from 57.27% to 80.69%. This comparative study provides scientific evidence to support the traditional use of Lamiacae plant species for medical purposes as anti - inflammatory and anti - proliferative medicines.

Los triterpenos son metabolitos secundarios muy importantes, con una amplia diversidad estructural y un rol significativo en la farmacia y la medicina. En esta investiga ción, se realizó un estudio comparativo de las actividades farmacológicas de las fracciones de triterpenos obtenidas de varias especies de plantas pertenecientes a la familia Lamiaceae. La actividad antiproliferativa in vitro se realizó mediante un ensayo estándar de proliferación basado en sales de tetrazolio. Se determinó la actividad antinflamatoria de las fracciones de triterpeno s mediante un ensayo de inhibición de desnaturalización de la albúmina. En general, las fracciones de triterpeno s obtenidas de las plantas pertenecientes a la familia Lamiaceae mostraron una actividad antiproliferativa y antinflamatoria fuerte. La fracción de triterpeno de Folium Rosmarini mostró la actividad antiproliferativa más fuerte (rango GI 50 entre 4 y 37 µg/m L ) y la más f uerte actividad antinflamatoria en el rango de 57,27% a 80,69%. Este estudio comparativo provée evidencia científica para apoyar el uso tradicional de especies de plantas Lamiaceae para usos médicos como medicinas antinflamatorios y antiproliferativas.

Application of direct peptide reactivity assay for assessing the skin sensitization potential of essential oils.

Plant-derived products are frequently found as ingredients in cosmetics. However, the current data show non-neglectable skin sensitizing potential of these preparations suggesting an urgent need for data regarding their health safety profile. The aim of this study was to assess the skin sensitization potential of commercial essential oils by selected Lamiaceae species (Lavandula angustifolia, Melissa officinalis, Mentha longifolia, Thymus vulgaris, Salvia officinalis, and Rosmarinus officinalis) using a chemistry-based Direct Peptide Reactivity Assay (DPRA) in order to predict their potential allergic properties. In the DPRA assay, nucleophile-containing synthetic peptides (cysteine peptide and lysine peptide) were incubated with the test substance for 24 h. Depletion of the peptide in the reaction mixture was measured by high-pressure liquid chromatography (HPLC) using UV detection and the average peptide depletion data for cysteine and lysine was then calculated. Menthae longifoliae aetheroleum showed no or minimal reactivity with 4.48% cysteine depletion, Rosmarini aetheroleum and Salviae aetheroleum showed low reactivity with the 12.79% and 15.34% of cysteine depletion, respectively, while the other analyzed essential oils showed moderate reactivity with the cysteine depletion between 23.21 and 48.43%. According to DPRA predictive analysis, only Menthae longifoliae aetheroleum can be classified as negative, while all other essential oils may be classified as positive, thus having the potential to cause skin sensitization.

Stability and Removal of Benzophenone-Type UV Filters from Water Matrices by Advanced Oxidation Processes.

Benzophenone (BP) type UV filters are common environmental contaminants that are posing a growing health concern due to their increasing presence in water. Different studies have evidenced the presence of benzophenones (BP, BP-1, BP-2, BP-3, BP-4, BP-9, HPB) in several environmental matrices, indicating that conventional technologies of water treatment are not able to remove them. It has also been reported that these compounds could be associated with endocrine-disrupting activities, genotoxicity, and reproductive toxicity. This review focuses on the degradation kinetics and mechanisms of benzophenone-type UV filters and their degradation products (DPs) under UV and solar irradiation and in UV-based advanced oxidation processes (AOPs) such as UV/H2O2, UV/persulfate, and the Fenton process. The effects of various operating parameters, such as UV irradiation including initial concentrations of H2O2, persulfate, and Fe2+, on the degradation of tested benzophenones from aqueous matrices, and conditions that allow higher degradation rates to be achieved are presented. Application of nanoparticles such as TiO2, PbO/TiO2, and Sb2O3/TiO2 for the photocatalytic degradation of benzophenone-type UV filters was included in this review.

From Heart Murmur to Echocardiography - Congenital Heart Defects Diagnostics Using Machine-Learning Algorithms.

The most common clinical sign in pediatric cardiology is heart murmur, which can often be uncharacteristic. The aim of this research was to present the results of development of a classifier based on machine learning algorithms whose purpose is to classify organic murmur that occur in congenital heart defect (CHD). The study is based on the data collected at Pediatric Clinic, Clinical Center University of Sarajevo during three-year period. Totally, 116 children aged from 1 to 15 years were enrolled in the study. Input parameters for classification are parameters obtained during basic physical examination and assessment of patient. First, analysis of relevance of the feature for classification was done using InfoGain, GainRatio, Relief and Correlation method. In the second step, classifiers based on Naive Bayes, Logistic Regression, Decision Tree, Random Forest and Support Vector Machine were developed and compared by performance. The results of this research suggest that high accuracy (>90%) classifier for detection of CHD based on 16 parameters can be developed. Such classifier with appropriate user interface would be valuable diagnostic aid to doctors and pediatricians at primary healthcare level for diagnostic of heart murmurs.