Search Results (3)

Kadsura coccinea is a traditional Chinese medicine whose roots have long been used to treat various ailments, but little is known about the efficacy of its leaves. In this study, the antidiabetic activity of K. coccinea leaf extract (KCLE) was determined, the main components of KCLE were identified using UPLC-TOF-MS, and network pharmacology and molecular docking were integrated to elucidate the antidiabetic mechanism of KCLE. The results showed that KCLE effectively increased the glucose consumption of IR-HepG2 cells through pyruvate kinase (PK) and hexokinase (HK), promoted glycogen synthesis, and inhibited α-glucosidase and α-amylase activities. KCLE also improves diabetes by regulating AKT1, TNF, EGFR, and GSK3β. These targets (especially AKT1 and TNF) have a high binding affinity with the main active ingredients of KCLE (rutin, luteolin, demethylwedelolactone, maritimetin, and polydatin). Pathway enrichment analysis showed that the antidiabetic effect of KCLE was closely related to the PI3K-Akt signaling pathway, MAPK signaling pathway, AGE-RAGE signaling pathway, and FoxO signaling pathway. These findings provide a theoretical basis for promoting the pharmacodynamic development of K. coccinea and its application in treating diabetes. Full article

The growing risk of antimicrobial resistance besides the continuous increase in the number of cancer patients represents a great threat to global health, which requires intensified efforts to discover new bioactive compounds to use as antimicrobial and anticancer agents. Thus, a new set of pyridothienopyrimidine derivatives 2a,b–9a,b was synthesized via cyclization reactions of 3-amino-thieno[2,3-b]pyridine-2-carboxamides 1a,b with different reagents. All new compounds were evaluated against five bacterial and five fungal strains. Many of the target compounds showed significant antimicrobial activity. In addition, the new derivatives were further subjected to cytotoxicity evaluation against HepG-2 and MCF-7 cancer cell lines. The most potent cytotoxic candidates (3a, 4a, 5a, 6b, 8b and 9b) were examined as EGFR kinase inhibitors. Molecular docking study was also performed to explore the binding modes of these derivatives at the active site of EGFR-PK. Compounds 3a, 5a and 9b displayed broad spectrum antimicrobial activity with MIC ranges of 4–16 µg/mL and potent cytotoxic activity with IC₅₀ ranges of 1.17–2.79 µM. In addition, they provided suppressing activity against EGFR with IC₅₀ ranges of 7.27–17.29 nM, higher than that of erlotinib, IC₅₀ = 27.01 nM. Full article

Introduction: Dacomitinib is an epidermal growth factor receptor (EGFR) inhibitor approved for the treatment of metastatic non-small cell lung cancer (NSCLC) in the first line in patients with EGFR activating mutations. Dacomitinib is taken orally once daily at 45 mg with or without food, until disease progression or unacceptable toxicity occurs. Oncology patients often can develop gastroesophageal reflux disease (GERD), which may require management with an acid-reducing agent. Proton pump inhibitors (PPIs), such as rabeprazole, inhibit sodium-potassium adenosine triphosphatase (H⁺/K⁺-ATPase) pumps that stimulate acid secretion in the stomach and have a prolonged pharmacodynamic effect that extends beyond 24 h post-administration. The aim of this work was to characterize the absorption of dacomitinib via modeling with a particular interest in quantifying the impact of rabeprazole on the pharmacokinetics (PK) of dacomitinib. Materials and Methods: The pooled dataset consisted of five clinical pharmacology healthy volunteer studies, which collected serial pharmacokinetic concentration-time profiles of dacomitinib. Non-linear mixed effects modeling was carried out to characterize dacomitinib pharmacokinetics in the presence and absence of the concomitant use of a PPI, rabeprazole. Several absorption models, some more empirical, and some more physiologically based, were tested: transit compartment, first-order absorption with and without lag time, and variations of combined zero- and first-order absorption kinetics models. Results: The presence of a PPI was a significant covariate affecting the extent (F) and rate (ka) of dacomitinib absorption, as previously reported in the dedicated clinical study. A transit compartment model was able to best describe the absorption phase of dacomitinib. Full article