Search

In this study, the impact of glucocorticoid, betamethasone dipropionate on enzyme activity in vitro and its effects on hematological parameters in vivo was investigated. The immobilized catalase, crucial for cell oxidative stress response via hydrogen peroxide reduction, exhibited a robust electrocatalytic response, maintaining its biological activity. The in vitro inhibition kinetics of catalase, as determined by electrocatalytic methods and expressed using Lineweaver-Burke diagrams, revealed an uncompetitive type of inhibition with altered Imax and Km in the presence of a range of betamethasone dipropionate concentrations. The in vivo experiments conducted on Rattus norvegicus demonstrated significant alterations in hematological parameters following betamethasone dipropionate administration. These changes included a decrease in erythrocyte count, an increase in hemoglobin, a reduction in mean corpuscular volume (MCV), and an elevation in mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC). Notably, the leukocyte counts substantially increased. The observed hematological shifts suggest an impact of betamethasone dipropionate on the hematopoietic system, reinforcing the need for cautious corticosteroid administration. The findings underline the necessity for judicious corticosteroid treatment, acknowledging both enzymatic and systemic repercussions. [ABSTRACT FROM AUTHOR]

In this study, the impact of glucocorticoid, betamethasone dipropionate on enzyme activity in vitro and its effects on hematological parameters in vivo was investigated. The immobilized catalase, crucial for cell oxidative stress response via hydrogen peroxide reduction, exhibited a robust electrocatalytic response, maintaining its biological activity. The in vitro inhibition kinetics of catalase, as determined by electrocatalytic methods and expressed using Lineweaver-Burke diagrams, revealed an uncompetitive type of inhibition with altered Imax and Km in the presence of a range of betamethasone dipropionate concentrations. The in vivo experiments conducted on Rattus norvegicus demonstrated significant alterations in hematological parameters following betamethasone dipropionate administration. These changes included a decrease in erythrocyte count, an increase in hemoglobin, a reduction in mean corpuscular volume (MCV), and an elevation in mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC). Notably, the leukocyte counts substantially increased. The observed hematological shifts suggest an impact of betamethasone dipropionate on the hematopoietic system, reinforcing the need for cautious corticosteroid administration. The findings underline the necessity for judicious corticosteroid treatment, acknowledging both enzymatic and systemic repercussions.

Ten novel 4-esterchalcones, licochalcone analogues, were strategically synthesized to study the effect of electro-donating or electro-withdrawing substituents in the aryl enone moiety on their pharmacological and photoprotective properties. 4-Esterchalcones had their drug-like character evaluated, which demonstrated positive characteristics for the development of novel drug candidates. In the in vitro antimicrobial evaluation, isovaleryl 4-esterchalcones showed activity against strains of Staphylococcus aureus, Candida albicans and C. tropicalis with minimum inhibitory concentration (MIC) in the range of 2.64-3.32 µmol mL−1, and the isobutyryl 4-esterchalcone 5d (4'-Br) presented antimicrobial activity against all strains tested, with a MIC of 2.74 µmol mL−1. In the UV-Vis study, λmax were observed at 312-327 nm, the UVB range, mainly. The best SPF-UVB results ranged from 18.04 to 21.06, with high εmax values, indicating that 4-esterchalcones have the potential to act as sunscreens. Furthermore, along with the environmental concern, halogenated compounds demonstrated slightly toxic on Artemia salina. [ABSTRACT FROM AUTHOR]

1,5-Benzothiazepines represent key scaffolds in medicinal chemistry because of their applicability in a wide variety of pharmaceuticals. Many cardiovascular, antidepressant, and antipsychotic drugs on the market accommodate this privileged structure, but the biological effects of 1,5-benzothiazepines are much more diverse, including enzyme inhibitory, antimicrobial, central nervous system depressant, anti-inflammatory, and anticancer activity. The introduction of a heterocyclic substituent onto a chemical structure can be beneficial in terms of bioactivity and drug-like properties. In this review, the biological activities of 1,5-benzothiazepines with and without heterocyclic substituents are discussed and compared. In some cases, the addition of a heterocycle proved to be beneficial for enhancing activity, especially the introduction of a 2-thienyl group, and also the position of heteroatoms in the substituent can have an impact on the overall properties of the resulting compounds. [ABSTRACT FROM AUTHOR]

ObjectivesThis study aimed to gain insights into pediatric clinical trials conducted in children's hospitals in China and provide valuable references for the development of children's hospitals and the research and development of pediatric drugs.MethodsA comprehensive search was performed on the Chinese Clinical Trial Registry (Chi CTR) and ChinaDrugTrials.org.cn to collect information on all clinical trials involving subjects under 18 years, including those conducted in children's hospitals. The retrieval period was extended until 31 December 2022.ResultsA total of 459 pediatric clinical trials were collected, comprising 299 from Chi CTR and 160 from the Drug Clinical Trial Registration and Information Publicity Platform (Information Platform). Post-marketing drug studies and phase III clinical trials accounted for the majority of research stages. These trials covered a wide range of diseases/systems, with a particular focus on respiratory system disorders, tumors, endocrine disorders, and nutritional or metabolic diseases. Chemical drugs constituted the most extensively studied category, while traditional Chinese medicine/natural drugs received comparatively less attention. Clinical trial activities were primarily geographically focused on the eastern coastal regions of China, with multicenter trials being the most predominant. Ethics committee approval was obtained for 427 studies.ConclusionThe pediatric clinical trials conducted by children's hospitals in China have shown an overall upward trend; however, there is limited research focusing on traditional Chinese medicine, along with significant regional and institutional imbalances. Furthermore, there is still room for improvement regarding ethical review processes. It is recommended that children's hospitals enhance their scientific research capabilities while optimizing resource allocation to meet medical service demands effectively. Additionally, fostering more research-focused children's hospitals will contribute to the high-quality development of children's health in China.

4-(2-Methyloxazol-4-yl)benzenesulfonamide was synthesized by the reaction of 4-(2-bromoacetyl)benzenesulfonamide with an excess of acetamide. The compound was evaluated as a potential inhibitor of human monoamine oxidase (MAO) A and B and was found to inhibit these enzymes with IC50 values of 43.3 and 3.47 μM, respectively. The potential binding orientation and interactions of the inhibitor with MAO-B were examined by molecular docking, and it was found that the sulfonamide group binds and interacts with residues of the substrate cavity. 4-(2-Methyloxazol-4-yl)benzenesulfonamide showed no cytotoxic effect against human stromal bone cell line (HS-5) in the concentration range of 1–100 µmol. Thus, the new selective MAO-B inhibitor was identified, which may be used as the lead compound for the development of antiparkinsonian agents. [ABSTRACT FROM AUTHOR]

Tetrahydropyridin-4-ylidene salts with benzyl and dibenzyl substitution showed good antiprotozoal activity. This paper reports the synthesis of analogues with longer side chains. They were investigated for their antiprotozoal activities as well as for their cytotoxicity using microplate assays. The most active compounds showed activity against Trypanosoma brucei rhodesiense in concentrations < 0.06 µM. A series of compounds was active against Plasmodium falciparum NF54 in low nanomolar concentration and exhibited outstanding selectivity. The influence of substitution pattern and chain length on the antiprotozoal potencies were analyzed and structure–activity relationships were given. New compounds were characterized by FT-IR, HRMS, and NMR spectroscopy. [ABSTRACT FROM AUTHOR]

Warfarin is the most prevalent anticoagulant which prevents blood coagulation as an antagonist of vitamin K. However, its high doses can result in several side effects. Accordingly, checking its level in human blood is of great importance in preventing overdose issues. Therefore, in this research, we proposed an easy-to-use and sensitive electrochemical device using a carbon paste electrode for measuring warfarin. Cyclic voltammetry (CV) and field emission scanning electron microscope were employed for monitoring the electrochemical behavior and surface morphology of the applied electrode, respectively. In addition, with the aim of achieving a better outcome, CV was employed to optimize pH and according to the results pH 4.5 was considered as the optimal value. Moreover, the effect of potential scan rate was studied using CV and the reaction possible mechanism was drawn. Furthermore, the selectivity of the constructed sensor was evaluated through investigation of the interfering materials effects and results (RSD values of 0.8–2.1%) demonstrated that the proposed device has considerable selectivity toward warfarin. The fabricated electrochemical device demonstrated desirable sensitivity with a linear response in the warfarin concentration range, the limit of detection and the limit of quantification of 3 × 10–5 to 3 × 10–3 M, 3.15 × 10–7, and 1.05 × 10–6 M, respectively. Given the obtained results, the fabricated device was successfully employed for measuring warfarin in real samples. Based on the RSD value (2.5%), it can be deduced that the fabricated sensor is a promising tool for online monitoring of warfarin in the near future. [ABSTRACT FROM AUTHOR]

Herein, the phase partitioning of triton X-100 (TX-100) and ceftriaxone sodium trihydrate (CTS) drug mixture in aqueous solutions of sodium salts was thoroughly investigated. The sodium carbonate (Na2CO3), sodium nitrate (NaNO3), sodium oxalate (Na2C2O4), and sodium phosphate (Na3PO4) were used to explore the effect of sodium salts on the cloudy creation of the mixture of TX-100 and applied drug. The CTS is a broad-spectrum cephalosporin antibiotic drug that is extensively utilized to cure bacterial diseases. The CP values of employed system were attained to be lessened by increasing the concentration of sodium salts (Na salts) and followed the pattern: CP aq. NaNO 3 > CP aq. Na 3 PO 4 > CP aq. Na 2 CO 3 > CP aq. Na 2 C 2 O 4 . The estimated several thermodynamic entities ( Δ G c 0 , Δ H c 0 , and Δ S c 0 ) change of phase partitioning of TX-100 + CTS drug is the measurement of interactions that exist between TX-100 and CTS in aquatic Na-salts environments. The calculated ( Δ G c 0 ) values were positive in the studied inspections, which demonstrated the nonspontaneous process of phase partitioning for the investigating system in aq. Na-salts media. The enthalpy–entropy compensation variables associated with the clouding process of TX-100 + CTS mixture in H2O + salts media were also calculated and interpreted in a detailed way. The operating forces between TX-100 and CTS are electrostatic and hydrophobic, which is evident from the values of Δ H c 0 and Δ S c 0 . [ABSTRACT FROM AUTHOR]

This special issue focuses on computational model for drug research regarding drug bioactivity prediction, drug-related interaction prediction, modelling for immunotherapy and modelling for treatment of a specific disease, as conveyed by the following six research and four review articles. Notably, these 10 papers described a wide variety of in-depth drug research from the computational perspective and may represent a snapshot of the wide research landscape. [ABSTRACT FROM AUTHOR]

4-(2-Methyloxazol-4-yl)benzenesulfonamide was synthesized by the reaction of 4-(2-bromoacetyl)benzenesulfonamide with an excess of acetamide. The compound was evaluated as a potential inhibitor of human monoamine oxidase (MAO) A and B and was found to inhibit these enzymes with IC50 values of 43.3 and 3.47 μM, respectively. The potential binding orientation and interactions of the inhibitor with MAO-B were examined by molecular docking, and it was found that the sulfonamide group binds and interacts with residues of the substrate cavity. 4-(2-Methyloxazol-4-yl)benzenesulfonamide showed no cytotoxic effect against human stromal bone cell line (HS-5) in the concentration range of 1–100 µmol. Thus, the new selective MAO-B inhibitor was identified, which may be used as the lead compound for the development of antiparkinsonian agents.

The synthesis of novel pyrazolothienopyridinone derivatives as potential GABAA receptor modulators was performed and is herein described. A crucial step of the synthesis involving handling unstable aminothiophenes was managed via two different synthetic strategies delivering a set of 8 target compounds. [ABSTRACT FROM AUTHOR]

The acid–base equilibria of six ACE inhibitors (ACEIs), captopril, cilazapril, enalapril, lisinopril, quinapril, and ramipril, were investigated in the presence of micelles of nonionic surfactant Brij 35. The pKa values were potentiometrically determined at 25 °C and at a constant ionic strength (0.1 M NaCl). The obtained potentiometric data were evaluated in the computer program Hyperquad. On the basis of the shift in the pKa values (ΔpKa) determined in micellar media in relation to the pKa values previously determined in "pure" water, the effect of Brij 35 micelles on ACEIs ionization was estimated. The presence of nonionic Brij 35 micelles caused a shift in the pKa values of all ionizable groups of the investigated ACEIs (ΔpKa from − 3.44 to + 1.9) while shifting the protolytic equilibria of both acidic and basic groups toward the molecular form. The Brij 35 micelles expressed the most pronounced effect on the ionization of captopril among the investigated ACEIs and stronger effect on the ionization of amino than on the ionization of carboxyl groups. The obtained results suggest that ionizable functional groups of ACEIs are involved in interactions with palisade layer of nonionic Brij 35 micelles, which potentially can be considered in physiological conditions. Distribution diagrams of the investigated ACEIs equilibrium forms as a function of pH indicate that the change in distribution is most strongly expressed in pH range 4–8, which includes biopharmaceutically important pH values. [ABSTRACT FROM AUTHOR]

3-(3,4-Dichlorophenyl)-5-(1H-indol-5-yl)-1,2,4-oxadiazole was synthesized via the condensation of 3,4-dichlorobenzamidoxime and methyl 1H-indole-5-carboxylate using a superbasic medium (NaOH/DMSO). The compound was tested as a potential inhibitor of human monoamine oxidase (MAO) A and B. It demonstrated a notable inhibition with an IC50 value of 0.036 μM for the MAO-B and isoform specificity. The product was characterized by 1H-NMR, 13C-NMR, and HRMS. In conclusion, the new active MAO-B inhibitor may serve as a candidate for the future discovery of therapeutic agents for neurodegenerative disorders such as Parkinson's disease. [ABSTRACT FROM AUTHOR]

Several 1-benzyl and 1,3-dibenzyl derivatives of tetrahydropyridinylidene salts with differing electron withdrawing substituents at the aromatic residues have been prepared. In addition, the amine moiety in position 4 was varied. The new compounds were investigated for their antiplasmodial and antitrypanosomal activities as well as for their cytotoxicity. They were characterized using FT-IR, HRMS and NMR spectroscopy. Structure–activity relationships including reported compounds are discussed. [ABSTRACT FROM AUTHOR]

3-(3,4-Dichlorophenyl)-5-(1H-indol-5-yl)-1,2,4-oxadiazole was synthesized via the condensation of 3,4-dichlorobenzamidoxime and methyl 1H-indole-5-carboxylate using a superbasic medium (NaOH/DMSO). The compound was tested as a potential inhibitor of human monoamine oxidase (MAO) A and B. It demonstrated a notable inhibition with an IC50 value of 0.036 μM for the MAO-B and isoform specificity. The product was characterized by 1H-NMR, 13C-NMR, and HRMS. In conclusion, the new active MAO-B inhibitor may serve as a candidate for the future discovery of therapeutic agents for neurodegenerative disorders such as Parkinson’s disease.

Fluorine incorporation into organic molecules is often beneficial to their absorption, distribution, metabolism, and excretion (ADME) properties or bioactivity. As a consequence, organofluorine compounds have become quite common amongst drugs and agrochemicals, and their preparation is a highly important topic in both synthetic organic chemistry and pharmaceutical chemistry. One of the newly developed methods for accessing organofluorine compounds is Pd‐catalyzed arylfluorination of alkenes. It is an olefin difunctionalization process that simultaneously introduces an aryl group and a fluorine atom into an alkene framework. This review provides a concise overview of this powerful and versatile method. [ABSTRACT FROM AUTHOR]

Three simple, sensitive, precise, and rapid spectrophotometric methods are developed and optimized for the assay of vardenafil in pharmaceutical formulations. The procedures are ascertained on the oxidation of vardenafil with a slight excess of N-bromosuccinimide (NBS), and the unreacted oxidant is estimated by evaluating the amount of the unconsumed NBS by reacting with a fixed amount of safranin (method A), crystal violet (method B), and aniline blue (method C) in an acidic medium by measuring the absorbance at 530, 600, and 610 nm, respectively. In all the methods, the amount of NBS consumed corresponds to the amount of the drug. Beer's law range, Sandell's sensitivity, and the corresponding molar absorptivity values of 1.1104 × 104, 1.0305 × 104, and 6.217 × 103 L/mol × cm for methods A, B, and C are calculated. The limits of detection and quantification are evaluated. The methods are also evaluated statistically by means of Student's t-test and F-test. The results show excellent agreement and insignificant difference between the proposed methods and the reference method. The developed methods are successfully applied to the assay of Vardenafil in pure and dosage forms, and no interference is observed from common excipients present in pharmaceutical formulations. [ABSTRACT FROM AUTHOR]

The overproduction of pro-inflammatory mediators is controlled by leukotrienes, viz. the 5-lipoxygenase inhibitors. These hold therapeutic importance in the treatment of a range of diseases such as rheumatoid arthritis, asthma, inflammatory bowel infection, and some forms of cancer. Owing to this, there has been an increase in the exploration of competent therapeutic agents meant for protein 5-lipooxygenase and at present, this practice is largely dependent on Quantitative Structure–Activity Relationship (QSAR). Nucleophilicity index is a significant electronic parameter which plays a crucial part in such studies. In this work, QSAR models are developed for some derivatives of benzoquinone in terms of nucleophilicity index invoking regression approach. The study entails prediction of inhibitory activity in terms of inhibitory concentration. Robustness and predictability of the nucleophilicity index–QSAR model is tested through cross-validation and test set activity prediction. Satisfactory results are produced by the model presenting the reliability of using nucleophilicity index as descriptor for inhibitory activity studies. It is, however, recommended that for future studies the above descriptor should be employed together with other relevant descriptors. [ABSTRACT FROM AUTHOR]