Ginsenoside Rb1 as a multi-target modulator in heart failure: Mechanistic insights into extracellular remodeling and transcriptional pathways from network pharmacology, molecular dynamics, and binding free energy analyses.

Ethnopharmacological basis and combined protection of intestinal barrier function by fucoidan from Sargassum thunbergii and chito-oligosaccharides in DSS-induced colitis.

Synthesis, spectral characterization, and cholinesterase inhibitory evaluation of benzothiazole-linked oxadiazole derivatives as potential anti-Alzheimer's agents.

The mucosal protective agent, bismuth potassium citrate, is used for treatment of chronic gastritis and gastric stress conditions, including heartburn and acid reflux. 1) To establish and validate a new inductively coupled mass spectrometry (ICP-MS) analytical method for the determination of bismuth metal in human plasma; and 2) to determine the systemic absorption and safety characteristics of bismuth following the administration of bismuth potassium citrate granules (test drug) and bismuth potassium citrate tablets (reference drug) in healthy Chinese subjects. A single-center, randomized, open-label, two-drug, single-dose, two-cycle, double-crossover pharmacokinetics study was carried out in a cohort of 24 healthy adult subjects in the fasting state. Subjects meeting the inclusion criteria were randomly assigned to the first cycle in ascending order of screening number obtained prior to dosing. The randomization table assigned subject either to the TR-group (test-reference cycle) or the RT group (reference-test cycle) where each group contained a total of 12 subjects. Subjects recruited but not completing the study, or in whom the data sets were incomplete, were not replaced. Using this study design, all subjects received a single dose of both preparations in the fasting state whereby 12 subjects received the drugs in the order RT and 12 subjects in the order TR, with a washout period of 7 days between each drug administration cycle, respectively. Pharmacokinetic parameters (concentration maximum (Cmax), AUC0-t, and area under the concentration-time curve to infinity (AUC0-∞) were analyzed using a linear mixed-effects model after natural log transformation. The lower limit of the 90% confidence intervals for the geometric mean ratio (test preparation/reference preparation) were below 100%, and the bioavailability of the test formulation (granules) was markedly superior to that for the reference formulation (tablets) where values for Cmax, AUC0-t, and AUC0-∞ after natural log transformation were 5.44, 12.82, 10.86, 22.44, and 13.79%, 27.42%, respectively. The systemic absorption of bismuth metal from the granules was not greater than that for the tablets. Although the bioavailability of the granules was markedly superior to tablets, the systemic absorption of bismuth metal from the two formulations was similar, and there was no evidence for a difference in the safety characteristics.

Tailored pyrrole-based imidazothiazole scaffolds: Synthetic elaboration, enzyme kinetic profiling and DFT-guided molecular docking toward Antidiabetic therapeutics.

Investigations on isatin-pyrimidinone hybrids as novel lead compounds for selective inhibition of TrkA enzyme.

One pot synthesis of pyrazolo-piperazine-quinazoline hybrids: evaluation of anticancer activity, molecular docking and ADMET studies

Diabetes is a persistent metabolic disorder characterized by either a relative or absolute deficiency of insulin, leading to elevated blood glucose levels.The current study primarily aims to assess the efficacy of polyherbal mixtures (PHM) in combating diabetes induced by streptozotocin (STZ) in rat models.This model of type 2 diabetes is established through the intraperitoneal administration of a single dose of streptozotocin (50 mg/kg b wt) intraperitoneally in albino Wistar rats.Based on a comprehensive literature review, three specific plant barks Ficus bengalensis, Acacia arabica and Casuarina equistifolia have been selected for their potential antihyperglycemic properties.The barks were subjected to hydroalcoholic extraction using a Soxhlet apparatus.The resulting extracts are then combined in three distinct ratios--1:2:3 (PHM I), 2:3:1 (PHM II), and 3:1:2 (PHM III).Following the induction of diabetes (4 days after streptozotocin injection), the rats were treated with the polyherbal mixtures orally for a duration of 21 days.Notably, PHM I demonstrates significant anti-hyperglycemic activity, as evidenced by reductions in all measured parameters compared to the diabetic control groups such as food and water intake (FI and WI), fasting blood glucose (FBG), Serum Glutamic-Oxaloacetic Transaminase (SGOT), Serum Glutamic Pyruvic Transaminase (SGPT), uric acid (UA), triglycerides (TG) and total cholesterol (TC).Metformin (220 mg/kg b wt) orally serves as a standard reference drug for comparison of anti-hyperglycemic effects across the different treatment groups.

Unveiling the RAAS-modulating terpenoid, Boerhadiffusene from Boerhavia diffusa L. and further envisage its potential anti-hypertensive activity through in silico and in vitro approaches.

Inhibitory potential of Morus alba leaf extract and its phytoconstituent against SARS-CoV-2 main protease: An integrative in silico and in vitro analysis.

Design, synthesis, in vitro and in silico evaluation of thiazole-hydrazine hybrids incorporating an isoindole-1,3-dione scaffold as potent α-glucosidase inhibitors.

Synthesis and anti-lung cancer evaluation of fused pyrazolo[3,4-b]pyridine linked isoxazoles and 1,2,3-triazoles: PEG-400 mediated one-pot reaction under microwave irradiation.

Synthesis and antiprotozoal activity of β-carboline-(piperazinyl)-1,3,5-triazine hybrids.

Design and synthesis of benzimidazole-based derivatives with antimicrobial activity: mechanistic insights into ROS-mediated oxidative damage, hemolytic assessment, and molecular docking studies.

In this work, a novel 2-(6-methyl-4-oxo-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-3-yl)acetonitrile 4 was used as starting material to create a new series of pyrazolo[3,4-d]pyrimidines. DFT calculations and spectroscopic data (IR, 1H NMR, 13C NMR, and MS) were used to determine the structure of newly generated products. HepG2, MCF7, and HeLa were specific human cell lines used to evaluate these new compounds. When compared to erlotinib four specific compounds 6c, 8b, 10 and 13c showed strong cytotoxic effects. When erlotinib was used as the reference drug, both 8b and 10 exhibited notable effectiveness against EGFRT790M/ HER2. A study of proliferation of breast cancer cell line showed that 8b increased in the percentage of DNA content in the G0-G1 phases, while 10 increased in the percentage of DNA content in the S phase. Furthermore, both 8b and 10 decreased in Bcl2 levels in breast cancer cells. Additionally, both compounds had favourable interaction with the EGFR tyrosine kinase domain (TKD) (PDB ID: 5JEB), with binding free energies (ΔGb) close to -9.2 and - 7.5kcal/mol, as revealed by molecular docking study. The molecular docking and ADME probe results were in accordance with the experimental data. In summary, the pyrazolo[3,4-d]pyrimidines 8b and 10 displayed bioactivities on EGFRT790M/ HER2, suggesting their potential possible preclinical candidates for future preclinical studies.

Colorectal cancer is the second leading cause of cancer-related mortality worldwide, highlighting the need for novel anticancer agents with fewer side effects. Endophytic actinobacteria (EA) are recognized as prolific producers of bioactive natural products. This study evaluated the anticancer potential of fractionated extracts from a novel endophytic actinobacterial strain, IKBG05 (genus Umezawaea), isolated from Cerasus microcarpa. Ethyl acetate extracts of submerged cultures were fractionated, and their cytotoxic effects were assessed against SW480 and HCT116 colorectal cancer cell lines. Among six fractions, F2 and F3' showed moderate cytotoxic effects consistent with early-stage screening of semi-purified fractions, with IC₅₀ values ranging from 188 to 416µg/mL. At the tested concentration, fraction F2 produced 2.48- and 2.67-fold higher growth inhibition in SW480 and HCT116 cells, respectively, compared with normal fibroblasts. F2 treatment was also associated with increased intracellular ROS levels and induction of apoptosis, particularly in HCT116 cells, comparable to the reference drug 5-fluorouracil.In parallel, genome mining of three available Umezawaea genomes identified 85 putative biosynthetic gene clusters (BGCs), suggesting considerable biosynthetic potential. This study provides the first genome-wide prediction of BGCs across currently available Umezawaea genomes and reports preliminary evidence of anticancer activity in extracts from strain IKBG05. These findings support further purification and characterization of the bioactive constituents.

Structure-Permeability relationships of Vitamin-B-Based quaternary ammonium salts for oral drug development.

The widespread presence of economically dominant pathogens has significantly hindered agricultural growth and productivity by affecting the quality and yield of crops. The recent deregistration of essential bactericides and nematicides have underscored the urgency for the development of novel agrochemical candidates. In response, N-7 alkylated xanthine derivatives were synthesized using various alkylbromides and characterized with the help of various spectroscopic techniques. The synthesized derivatives were explored for antioxidant, antibacterial, antifungal and antinemic properties. A comprehensive evaluation of antioxidant potential of synthesized compounds utilizing various models revealed that compound 7-decyl-1H-purine-2,6-(3H,7H)-dione (2j) exhibited strong antioxidant potential due to enhancement of electron-donating characterin reference to ascorbic acid. Furthermore, evaluation of antimicrobial activity against Dickeya sp., Xanthomonas campestris and Fusarium oxysporum, and antinemicactivity against Meloidogyne incognita, demonstrated that compound (2j), among other tested compounds, displayed noteworthy inhibitory activity against these pathogens as compared to reference drugs i.e. ciprofloxacin, gentamycin (antimicrobial activity) and carbofuran (antinemic activity). Also, in silico investigations were performed aiming for acetylcholine esterase enzyme inhibition activities to recognize novel interactions of the tested compounds with target binding sites of Meloidogyne incognita. The promising in vitro results warrant further validation under in vivo and field conditions. This research offers valuable insights that these compounds can serve as key precursors for future development of agrochemical agents for managing biotic stresses and improving crop productivity.

This study aimed to develop novel non-imidazole histamine H3 receptor (H3R) antagonists as potential antiseizure agents. We designed and synthesized a series of 2-aryloxazole derivatives (4a-4t) by relocating a phenyl group from the piperidine side chain to the oxazole core of a previous the lead compound (5g), aiming to optimize lipophilicity and receptor binding. Among the synthesized compounds, 4f exhibited the most potent H3R antagonistic activity (IC50 = 0.056 µM), superior to lead compound 5g and the reference drug Pitolisant (PIT). Compound 4f also demonstrated high selectivity over other histamine receptor subtypes (H1R, H2R, and H4R). In vivo, 4f showed significant and sustained antiseizure efficacy in the maximal electroshock (MES) model in mice (ED50 = 17.36mg/kg) and potently suppressed seizures in a zebrafish pentylenetetrazol (PTZ) model. Pharmacokinetic studies revealed favorable oral bioavailability (81.12%) and effective brain penetration (90min brain-to-plasma (B/P) ratio = 4.15) with progressive accumulation. Preliminary safety profiling indicated minimal neurotoxicity at therapeutic doses and a lower hERG channel inhibition risk compared to PIT. These results identify 4f as a potent, selective, and brain-penetrable H3R antagonist with robust antiseizure activity and a favorable preclinical profile, supporting its further development as a novel antiseizure agent.

Hydrazone-based ligands constitute multifunctional pharmacophores owing to their flexible coordination modes and tunable electronic properties. Upon metal complexation, these features modulate physicochemical characteristics and biological responses, enabling the development of metal-based therapeutics. This study reports the rational design, synthesis, structural characterization, and anti-inflammatory evaluation of a series of hydrazone ligands and their Cu(II) and Zn(II) complexes. Spectroscopic and crystallographic analyses confirmed tridentate coordination through azomethine nitrogen and carbonyl oxygen donors, leading to distorted octahedral geometries around the metal centers. In vitro cyclooxygenase inhibition assays showed that metal coordination significantly enhanced anti-inflammatory activity relative to the free ligands. The Cu(II) complexes [Cu(acbh)2] (3) and [Cu(bcbh)2] (5), along with the Zn(II) complex [Zn(bcbh)2] (6), exhibited notable COX-2 selectivity compared to the reference drug celecoxib. Among all compounds, complex 6 emerged as the most potent dual COX-1/COX-2 inhibitor, displaying a COX-2 IC50 value of 0.41 µM and a selectivity index of 307.32, indicating potential as a broad-spectrum anti-inflammatory agent. Molecular docking studies supported these results, revealing favorable binding energies and stable interactions of the metal complexes within COX active sites. Overall, these findings emphasize the role of metal coordination in enhancing enzyme binding and biological activity.