Bruton’s tyrosine kinase (BTK) is a clinically validated therapeutic target for autoimmune and lymphoproliferative disorders. In this study, we conducted a comprehensive computational analysis to evaluate the binding properties, structural stability, and drug-likeness of three investigational BTK inhibitors: Tolebrutinib, Poseltinib, and JDB175, in comparison with the approved reference drug, Ibrutinib. Density functional theory (DFT) calculations revealed that JDB175 possesses the highest electrophilicity index and a relatively narrow HOMO–LUMO energy gap among the investigated inhibitors, indicating its high chemical reactivity potential. Molecular docking studies demonstrated strong interactions for Tolebrutinib and JDB175 with key BTK residues (Cys481, Glu475, and Met477), with binding energies of −11.8 and −12.1 kcal/mol, respectively. Molecular dynamics simulations (200 ns) confirmed the structural stability of the Tolebrutinib and JDB175 complexes, consistent with their MM-PBSA free energy values (−48.05 and −47.28 kcal/mol, respectively). ADME/T analysis showed favorable pharmacokinetic profiles for all candidates. These findings suggest that Tolebrutinib and JDB175 are promising BTK inhibitor candidates with optimal interaction profiles and drug-like properties, supporting their potential for further development in BTK-targeted therapy.
In this study, three bis-thioureas (abbreviated as SJ1, SJ2, and SJ3) were synthesized and theirantihyperlipidemic effects were assessed in mitigating high-fat diet (HFD)-induced metabolicdisturbances in rat model. Among the tested compounds, SJ3 was more potent as antioxidantagent with IC50=115.23 μg/mL against DPPH whereas against ABTS, 49.6 and 81% activities wererecorded for lowest and highest tested concentrations (62.5 and 1000 μg/mL). In comparison tocontrol (HFD) and standard drug administered animal groups, SJ3 reduced total cholesterol (101.8,211.1, and 94.5 mg/dL), triglycerides (95.8, 208.3, and 84.5 mg/dL), LDL (134.7, 56.8, and 45.8mg/dL), and HDL (32.6, 18.7, and 43.1 mg/dL) levels. Significant reduction in ALT, ALP, uric acid, urea, creatinine, and body weight were also observed for SJ3 treated group. Moreover, dockingstudies confirmed binding of the test compounds with five key protein targets. Overall, SJ3 demonstrated the highest binding affinity with 1HW9 (-8.6 kcal/mol), followed by orlistat (-8.1kcal/mol). SJ3 demonstrated the highest binding affinity with 3VI8 (-9.9 kcal/mol) and 4EWS (-8.9kcal/mol), while ranked second after standard drug orlistat for 1LPB (-8.7 kcal/mol), and 7O7B(-6.4 kcal/mol). In silico pharmacokinetics (ADMET), and toxicity studies also supported SJ3 as the most effective compounds. The synthesized thioureas though possesses antihyperlipidemicpotentials, further research is needed to validate the findings in clinical practices.
A series of novel small-molecule inhibitors targeting c-Met was designed, synthesized, and optimized based on high-throughput virtual screening of the lead compounds BMS-777607 and 17b. Biological activity evaluation revealed that most compounds demonstrated significant antiproliferation activity against A549 and HepG2 tumor cell lines. Among these compounds, 10a exhibited the most potent kinase inhibitory activity (IC50 = 0.31 μM). Compound 10a demonstrated strong apoptosis-inducing ability in A549 cells (IC50 = 1.38 μM) while showing negligible antiproliferative effects on the human normal liver cell line Chang liver (CCL13). Further investigation of the antitumor mechanism revealed that compound 10a inhibited the synthesis of key proteins, including PCNA, Cyclin D1, procaspase 3, BCL-2, and mitochondrial Cyt c in A549 cells. Additionally, it promoted the expression of cleaved caspase 3, BAX, and cytoplasmic cytochrome c, while inducing cell cycle arrest at the G2/M phase. Molecular docking studies demonstrated that 10a exhibited strong binding affinity to the ATP-binding site of c-Met. These findings suggest that compound 10a represents a promising lead molecule for further development of antitumor drugs.
A set of guidelines for the preparation and administration of injectable medications, along with incompatibilityalerts, was developed for their integration to the electronic prescription system of a university hospital.Descriptive study based on data analysis using descriptive statistical methods performed in MicrosoftExcel®. The information was obtained through a literature review using the Micromedex®, UpToDate®, Whitebook Clinical Decision® and Cognys Med® databases, from January 2023 to November 2024,with emphasis on the topic "medication administration." The guidelines and alerts were developed bytwo pharmacists: one was responsible for drafting the instructions and the other, for reviewing them.Subsequently, the collected information was entered into the electronic prescription system. The studyled to 179 standardized injectable medication presentations in the hospital. Specific instructions for thepreparation and administration of each medication were elaborated, as well as alerts for six medicationsthat require photoprotection and for other six medications that interact with PVC. It was also identified that10 medications should not be diluted in 0.9% sodium chloride and another 10 that should not be diluted in glucose due to incompatibility issues. The aim of implementing these guidelines and alerts integrated intothe electronic system is to reduce medication errors and to enhance treatments’ safety and effectiveness.
Vesicular drug delivery systems, including liposomes, niosomes, bilosomes, and transferosomes, haveemerged as advanced platforms for targeted and controlled drug delivery. These carriers are designedusing diverse preparation techniques such as thin film hydration, ethanol injection, reverse phaseevaporation, and advanced methods like spray drying and microfluidics. Each technique offers uniqueadvantages and limitations, influencing scalability, encapsulation efficiency, and industrial feasibility.The integration of emerging technologies has significantly improved the stability, reproducibility,and large-scale production of vesicular formulations, addressing key challenges in pharmaceuticaldevelopment. The growing interest in these systems has led to several marketed products, demonstratingtheir commercial viability. For instance, Doxil® (liposomal doxorubicin) and AmBisome® (liposomalamphotericin B) are widely used in oncology and antifungal therapy, respectively, showcasing theclinical benefits of liposomal formulations. Similarly, niosomal-based drug carriers like Niospan®(niacin extended-release) and ethosomal systems such as Nanomax® (for transdermal delivery) highlighttheir therapeutic potential across multiple domains. With continuous advancements, vesicular drugdelivery systems are poised to revolutionize modern therapeutics, offering enhanced bioavailability,targeted delivery, and improved patient compliance. This review provides a comprehensive overviewof preparation techniques, comparative analyses, and real-world applications, underscoring theirtransformative role in pharmaceutical sciences and future drug development.
