Macrocyclic histone deacetylase inhibitor-based near-infrared-responsive ionic nanomedicines for enhanced cancer therapy.

Identification and validation of glycosylation-related biomarkers in the hippocampus for Alzheimer's disease diagnosis and drug repurposing.

Integrated DIA proteomics and molecular docking studies on the potential anti-inflammatory mechanism of Anwulignan.

Novel benzimidazole-based thioamide derivatives as potential anticancer agents: synthesis, biological evaluation, and in silico studies.

Discovery of 1,2-dihydro-4-hydroxy-2-oxoquinoline-3-carboxamide derivatives as potent anticancer agents: Structure-based design, synthesis, mechanistic insights, target identification, and molecular docking studies.

Design, synthesis, and biological evaluation of Chromene-Phenylpiperazine-Chalcone hybrids as multi-target-directed ligands for the treatment of Alzheimer's disease.

Guaiacol counters renal fibrosis via BMP/ERK/Smad1/5/9 signaling in UUO-induced chronic kidney disease.

Chronic liver disease is a progressive, worldwide health crisis, with its incidence and prevalence increasing annually. It causes progressive liver injury and ultimately fibrosis. Globally, it is responsible for approximately 2 million deaths annually. Despite its growing prevalence, there is currently no approved, highly effective targeted therapy for managing liver dysfunction. Targeting caspase-3 activity may attenuate hepatocellular injury, reduce inflammation and oxidative stress, and thereby improve liver functional integrity. Ten cyclic curcumin analogues (2-11) were synthesized, followed by preliminary screening for caspase-3 inhibitory activity. Their structures were confirmed by spectral and microanalytical data. The most active triazole (4) and sulfonamide (5) analogues were further evaluated in vivo to assess their anti-inflammatory, antioxidant, and caspase-3 inhibitory effects in rat liver tissue. Molecular docking study was performed to confirm caspase -3 regulation. Radiation stability study was held. Results: Analogues 4 and 5 significantly improved biochemical and molecular markers associated with liver dysfunction, including reductions in inflammation, oxidative stress, caspase-3 activity, TNF-α, p53, and Bax levels, alongside modulation of Bcl-2 expression. The triazole analogue 4 and sulfonamide analogue 5 demonstrate promising hepatoprotective activity and may represent stable lead compounds for potential therapeutic management of liver dysfunction.

Assessment of the antimicrobial properties of novel azopyrazolo[1,5-a]pyrimidine derivatives targeting DNA gyrase enzyme: design, synthesis, and molecular docking studies.

• Three styryl-benzonitrile chromophores 3, 4 , and 5 were synthesized and characterized by IR, NMR, and MS tools. • The styryl-benzonitrile compounds display clear intramolecular charge-transfer behavior, which helps separate charge but also tends to suppress their fluorescence output. • The absorption spectra of styryl-benzonitriles disclosed the piperidinyl 3 had the highest Δ E max , while the emission showed the morpholino 4 . • The cytotoxic activity demonstrated compound 5 as the safest one toward normal cells. • In docking studies against Escherichia coli DNA gyrase B, chromophore 5 displayed the strongest binding energy Styryl-Benzonitrile chromophores 3, 4 , and 5 were synthesized from diethyl 4-cyanobenzyl phosphonate ( 1 ) and benzaldehyde derivatives ( 2 ) via the Horner-Wadsworth-Emmons reaction. The trans configuration of the synthesized chromophores 3 - 5 has been verified by the distinctive nitrile stretching band (at ∼2210 cm⁻¹) and coupling constants (J ≈ 15.5 Hz). The DFT studies indicated that the HOMO was located on the donor fragment and the LUMO was spread on the benzonitrile acceptor fragment, confirming the important intramolecular charge transfer (ICT). Chromophore 5 displayed the smallest HOMO-LUMO gap = 2.82 eV, which correlated well to red-shifted absorption (λ max = 393 nm) and emission (λ em = 561 nm). The absorption spectra of these probes in varied solvents revealed that the piperidinyl 3 had the highest Δ E max (+3.09 kcal.mol -1 ), however, their emission spectral data presented hybrid 4 as the most polarity-induced (Δ E max +3.56 kcal·mol -1 ). Biologically, chromophore 5 unveiled the highest cytotoxic effectiveness towards HepG2 cells (IC₅₀ = 19.04±0.13 μM), with a higher selectivity index (SI = 4.6). Docking studies on DNA gyrase B (PDB: 1HNY, resolution 1.59 Å) showed a good binding (S = -5.97 kcal·mol -1 ) with important H-bonding bindings with Arg195 and Asp300. As well, the pharmacokinetic profiles of the synthesized chromophores indicated that all probes have auspicious drug-likeness properties, rendering them suitable for further evaluation.

Traditional Chinese medicine for antipsychotic-induced hyperprolactinemia: A comprehensive review of ethnopharmacological foundations, mechanistic insights, and network pharmacology perspectives.

Herein, we report four new cationic ruthenium(II)-(p-cymene) racemic complexes (C1-C4) containing N,S-coordinated pyrazoline ligands. The contemplated organoruthenium compounds from dimeric Ru(II)-(η6p-cymene) chlorido moieties and pyrazoline-based ligands were synthesized and characterized using standard analytical, spectral and ESI-HRMS data. The pseudo-octahedral geometry, neutral bidentate N and S chelation of pyrazoline thiosemicarbazones, and cationic nature of all four complexes were confirmed through single-crystal X-ray diffraction (SC-XRD) study. The geometry of individual enantiomers of the respective enantiomeric pairs was optimized using density functional theory. Furthermore, frequency calculations, single-point calculations, frontier molecular orbital analysis and TD-DFT were also carried out. Biomolecular interactions of the complexes were investigated using UV-visible and fluorescence spectroscopy techniques with calf-thymus DNA (CT-DNA) and bovine serum albumin (BSA). Anticancer activity of the racemic complexes C1-C4 against human colorectal adenocarcinoma (HT-29) and human lung cancer (A549) cell lines assessed using MTT assay indicated the IC50 concentrations ranging from 15.39 to 21.86 µM and 17.29 to 24.29 µM for HT-29 and A549 cells, respectively, and the values are comparable to that of the positive control (cisplatin) and also the same assay was performed on human epithelial kidney cells (HEK-293) to determine the selectivity index of the complexes. As these four complexes possess similar molecular structures, based on the better selectivity index and promising in vitro performance, complex C2 was selected for more detailed anticancer assays. DAPI, DCFDA, and JC-I cellular staining assays, along with flow cytometry, were performed on C2-treated A549 cells. The complex C2 induced apoptosis through DNA damage, ROS generation, and mitochondrial depolarization. Molecular docking studies on the DFT-optimized R and S conformers of the complexes were undertaken towards a spectrum of cancer-related protein targets to validate their binding interactions. The complexes demonstrated favorable binding interactions with B-DNA, BSA, cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2), with high binding affinity values of -8.12, -6.6, -6.25 and -7.53 kcal mol-1, respectively. Simultaneously, binding interactions of the individual enantiomers (R and S) of the respective pairs of each complex towards the target proteins were also examined, but they did not vary greatly among the complexes.

Due to the limitations of platinum-based chemotherapeutics such as cisplatin, including severe toxicity and acquired drug resistance, the development of alternative metal-based agents with improved efficacy and reduced side effects has become a key goal in medicinal chemistry. Among these, organotin(IV) compounds have attracted considerable interest owing to their potent antibacterial and anticancer properties. Since the pharmacological activity, transport, and bioavailability of such metal-based drugs are strongly influenced by their binding to plasma proteins particularly human serum albumin (HSA) understanding these interactions is essential for evaluating their invivo behavior and therapeutic potential. This study investigates the binding behavior of the organotin(IV) complex [SnMe2Cl2(Me2phen)] with HSA under physiological pH (7.4), utilizing both spectroscopic techniques and molecular docking studies. Upon addition of the complex, a decrease in HSA absorbance was observed, suggesting an interaction between the complex and the protein. Fluorescence quenching data, along with the calculated Stern-Volmer (Ksv) and bimolecular quenching (kq) constants, indicated a static quenching mechanism. Thermodynamic parameters (ΔH° < 0 and ΔS° < 0) implied that hydrogen bonding forces and van der Waals forces predominantly govern the binding process. Site-selective displacement assays with site-specific markers, warfarin and ibuprofen, suggested that the complex may associate with both Sudlow's site I and site II of HSA. Circular dichroism (CD) spectroscopy revealed a reduction in the α-helical content of HSA upon complexation, indicating partial conformational changes in the protein structure. Molecular docking results supported the experimental findings and provided further insight into the binding mode of the complex with HSA.

Silver(I) complexes of 5,5-diethylbarbiturate and polypyridyl ligands: Structural, antimicrobial and molecular docking studies

Synthesis, characterization, molecular docking study, and preliminary anticancer study of a novel ligand: 4-(4-(quinolin-8-yloxy)-1, 2, 5-thiadiazol-3-yl) morpholine

Aromatic heterocycle substituted 2-hydrazinylthiazole Schiff bases: Antioxidant, antibacterial activities, DFT calculations, and molecular docking studies

Dihydrothiophene ureidoformamide derivatives are sulfur-containing heterocyclic frameworks that remain relatively underexplored for their anticancer potential, despite possessing structural features that may enable interactions with biological targets involved in tumor progression. In the present study, a series of these derivatives was synthesized, structurally characterized, and evaluated for their anticancer activity against HCT116 human colorectal carcinoma cells. Among the tested compounds, compound 7 exhibited notable antiproliferative activity, showing a faster reduction in cell index compared to the reference drug paclitaxel during the initial 24 h of treatment, along with a dose-dependent decrease in cell index. Flow cytometric analysis using Annexin V-FITC/PI staining revealed that compound 7 induced significant apoptotic cell death, reaching 62.89% after 24 h of treatment. Molecular docking studies further indicated favorable binding interactions of compound 7 with several cancer-related targets, including EGFR, VEGFR-2, and AKT1. Overall, the obtained results suggest that this family of compounds, particularly compound 7, may represent an interesting scaffold for further investigation in the development of anticancer agents.

The role of two different non-steroidal anti-inflammatory drugs, namely, mefenamic acid (MA) (2-[(2,3-dimethylphenyl)amino]benzoic acid) and aceclofenac (ACF) (2-[(2,6-dichlorophenyl)amino]phenyl acetoxyacetic acid), and their electrostatic interactions with bovine serum albumin (BSA) and adenine model systems have been studied. The binding affinity for drug formation depends primarily on the heterocyclic ring and functional groups. The hydrophobic interactions were also evaluated. The spectral properties of the interactions were investigated by UV-visible, fluorescence, FT-IR, cyclic voltammetry and molecular modelling methods. In addition, the Stern-Volmer plots for BSA and adenine with the drug molecules are shown. Moreover, the static quenching interaction, the binding constant (Ka) and the number of sites (n) have been determined. The binding efficiency is evaluated and compared on the basis of its E value. The free energy, van der Waals and hydrogen-bonding interaction values of BSA with the drugs are determined. In order to assess the electrochemical process, the scan rate is another important parameter, which has been determined by using cyclic voltammograms.

Colorectal cancer is one of the leading causes of cancer-related deaths and ranks third among them. Our efforts to develop new anticancer agents to treat this disease resulted in the synthesis of new isatin-based oxime ethers. The cytotoxic effects of these compounds against HCT116 were analyzed using MTT and Trypan Blue dye exclusion assays. A compound 10d has emerged as a lead compound with IC50 value of 22.31 ± 1.23µM. Even though this molecule is two-fold less active than reference drug 5-fluorouracil (5-FU), the pharmacophore of the compound 10d would be considered for future derivatisation as a notable anticancer agent, due to its safety profile against normal cell line HEK. The anticancer effect of compound 10d against colon cancer cells was demonstrated by cell shrinkage and detachment observed under bright-field microscopy. Furthermore, Hoechst/propidium iodide (PI) staining and acridine orange (AO)/PI staining analysis confirmed the induction of cell death. Treatment with compound 10d restrains colony formation ability and mitigates the migratory potential of colon cancer cells as observed by both foci formation and migration assay. Finally, we elucidated the possible mode of action of the lead molecule by in-silico analysis using molecular docking studies. Results unveiled that the lead compound exhibits anticancer potential probably by targeting Human Tankyrase-2 and Bruton's tyrosine kinase with high docking scores, as evident by in-silico modelling. The binding affinity of synthetic compounds against the protein targets 5BXU and 7LTZ was assessed by molecular docking experiments. The compound 10d demonstrated the greatest affinity for both targets (- 8.8 and - 7.9kcal/mol, respectively), whereas other compounds showed favourable binding energies. These findings suggest that compound 10d may serve as a promising lead for further biological evaluation.

This study aimed to design and synthesize novel 3-pentyl-substituted 1,2,4-triazole-5-thione Schiff base derivatives and evaluate their dual inhibitory potential against urease and α-glucosidase enzymes. The target compounds (6a-e) were synthesized via an ultrasound-assisted condensation method under mild conditions. Structural characterization was performed using Fourier Transform Infrared (FT-IR), 1H/13C nuclear magnetic resonance (NMR), and Liquid chromatography mass spectrometry (LC-MS) analyses. Enzyme inhibitory activities were evaluated using standard spectrophotometric assays, while molecular docking studies were conducted to investigate binding interactions. In silico absorption, distribution, metabolism, and excretion (ADME) properties were predicted using SwissADME. All compounds exhibited measurable inhibitory activity against both enzymes. Among them, compound 6c demonstrated the highest potency (urease IC50 = 14.14 ± 2.61 μg/mL; α-glucosidase IC50 = 13.14 ± 0.42 μg/mL), showing activity comparable to reference inhibitors. Docking analysis revealed favorable binding interactions, including hydrogen bonding and hydrophobic contacts, particularly for 6c. ADME predictions indicated favorable pharmacokinetic profiles for compounds 6a-6d. The results highlight the potential of triazole-Schiff base hybrids as dual-enzyme inhibitors, with compound 6c identified as a promising lead for further optimization.