Cornus mas L. is traditionally used for various medicinal purposes, although systematic data on its pharmacognostic properties are still limited. Considerable variation was observed among plant organs, so phenolic and flavonoid content varied by plant part, with location-related differences among samples, with the highest in leaf and fruit from Bijeljina and the lowest in leaf from Sarajevo. Antioxidant activity was much better in leaf and bark than in fruit. Extracts inhibited ESBL-producing Escherichia coli, with MICs mainly at 125 µg/mL; bark extract (Tuzla) showed 250 µg/mL and reduced biofilm formation. Leaf and bark extracts showed dose-dependent cytotoxicity against PC-9, MCF-7, and MDA-MB-231 cells, while fruit extracts were weaker. In human lymphocytes, bark (Bileća) and leaf (Tuzla) extracts decreased nuclear division and induced micronuclei at 200 µg/mL. Molecular docking indicated strong bacterial target binding for loganin and cornuside, supporting the antibacterial and antitumor potential of C. mas.

Marine natural products represent a diverse collection of structurally distinct metabolites, many of which have untapped therapeutic potential. This study screened 161 marine-derived coumarin and xanthene compounds for their binding affinity to the histamine H2 receptor and the gastric H+/K+-ATPase, the primary regulators of gastric acid secretion. Docking simulations were performed using curated structures of both targets, followed by an evaluation of the compounds for drug-likeness and predicted absorption, distribution, metabolism, and excretion (ADME) properties. Thirty-four compounds demonstrated a stronger predicted affinity for the H2 receptor than famotidine; however, only three compounds (1, 5, and 150) met all drug-likeness criteria, achieving quantitative estimates of drug-likeness (QED) values exceeding 0.67. Screening against the proton pump yielded 98 hits with higher affinity than soraprazan, with compound 150 being the only candidate to fulfill all medicinal chemistry filters. Interaction analysis indicated that compound 150 binds to the proton pump in a manner that largely overlaps with soraprazan. Density functional theory (DFT) calculations were utilized to characterize the electronic properties of the most promising compounds. ADME predictions suggested favorable permeability and a low risk for human ether-à-go-go-related gene (hERG) inhibition, although high plasma protein binding and the potential for cytochrome P450 (CYP) inhibition may require further optimization. These findings underscore the potential of pyranocoumarin compound 150, along with xanthene derivatives 1 and 5, as promising candidates for the development of new acid-suppressive agents.

Inflammation, oxidative stress, and androgen activity are key features in benign prostate hyperplasia (BPH). Risks associated with the long-term use of 5α-reductase inhibitors have led to the search for alternative therapies, including food supplements. This study investigates the effectiveness of the combination of pollen extracts, namely Graminex®G96® (G) and Teupol 25P (T), towards oxidative stress and inflammation on human macrophages and benign prostate hyperplasia cells (BPH-1), both of which are LPS stimulated. The Nrf2-dependent antioxidant intracellular cascade as well as the NF-ĸB-driven inflammatory cascades were analyzed. The anti-proliferative effect of G and T, alone and in association, were evaluated on prostatic adenocarcinoma cells (PC-3) and BPH-1 cells. Finally, the inhibitory activity of GT on 5α-reductase was investigated in PC-3 cells by measuring epiandrosterone amounts, with the 5α-reductase inhibitor finasteride administered for comparison. All experiments were conducted in triplicate; data are presented as mean values ± standard deviations. Statistical analysis was performed using one-way analysis of variance. Our work demonstrates that GT promotes Nrf2-dependent antioxidant responses and counteracts the NF-ĸB-driven pathway in macrophages. GT is effective in counteracting the expression of pro-inflammatory cytokines and the generation of reactive oxygen species by promoting HO-1-dependent antioxidant responses in BPH-1 cells. GT reduces PC-3 and BPH-1 proliferation when associated with finasteride through a statistically significant inhibition of 5α-reductase activity. Data obtained in vitro and in silico demonstrate the potential efficacy of a multitargeted approach in the treatment of BPH.

Benzoxazoles possess a wide range of therapeutic activities, including antimicrobial, antitumor, anti‐inflammatory, and other. Using in silico and in vitro approaches, we determined the potential antitumor activity of benzoxazoles synthesized from thymoquinone in diffuse large B‐cell lymphoma (DLBCL) cells. Molecular docking analysis showed strong binding affinities of benzoxazoles toward Akt and nuclear factor kappa B (NF‐κB) protein targets that promote cancer cell proliferation and survival and whose expression is linked to tumorigenesis of activated B‐cell (ABC) and germinal center B‐cell (GCB) DLBCL subtypes. WST‐8 assay showed the highest inhibitory activity of benzoxazole derivative bearing thiophene substituent in both DLBCL models. Western blot analysis indicated the inhibitory activity of selected compounds in HBL‐1 cells, with decreased p‐NF‐κB and p‐Akt protein expression, whereas treatment of DHL‐4 cells stimulated the expression of p‐Akt and p‐NF‐κB protein levels. These data suggest distinct, cell line‐dependent activities of the substances that potentially act through diverse oncogenic signaling pathways in DLBCL cells and activation of compensatory cell mechanisms that could be an important step for combinatorial treatment approaches.

Although COVID-19 is not a pandemic anymore, the virus frequently mutates, resulting in new strains and presenting global public health challenges. The lack of oral antiviral drugs makes it difficult to treat him, which makes the creation of broadly acting antivirals necessary to fight current and next epidemics of viruses. Using the molecular docking approach, 118 compounds derived from marine organisms and 92 previously synthesized compounds were screened to assess their binding affinity for the main protease and papain-like protease enzymes of SARS-CoV-2. The best candidates from the xanthene, benzoxazole, and coumarin classes were identified. Marine-derived compounds showed slightly better potential as enzyme inhibitors, though the binding affinities of synthesized compounds were similar, with the best candidates displaying affinity values between 0.2 and 0.4 mM. Xanthenes, among both marine origin and synthesized compounds, emerged as the most promising scaffolds for further research as inhibitors. The papain-like protease was found to be more druggable than the main protease. Additionally, all top candidates met the criteria for various drug-likeness properties, indicating good oral bioavailability and low risk of adverse effects. This research provides valuable insights into the comparative affinities of marine origin and synthesized compounds from the xanthene, coumarin, and benzoxazole classes, highlighting promising candidates for further in vitro and in vivo studies.

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint inflammation and destruction, leading to significant pain and disability. Adenosine deaminase (ADA) is identified as a biomarker for RA’s inflammatory process. This study aims to investigate the potential of flavonoids and phenolic acids to inhibit ADA activity (in silico) and evaluate their anti-inflammatory effects in a RA model (in vivo). Methods: The molecular docking study was conducted using YASARA Structure 19.12.14. software following the Auto Dock 4.2 protocol. A rat model with pristane-induced arthritis was used to test the anti-inflammatory effect of selected polyphenols. The consistency of the development of the rat model was evaluated through the following indicators artistic score, paw volume, and body weight. Quercetin was administered intragastrically at doses of 150 and 400 mg/kg over 15 days. The C-reactive protein (CRP) level in serum was measured with an automatic biochemical analyzer. Statistical analyses were performed using SPSS 29.0.2.0. Results: Molecular docking simulations showed flavonoids inhibited ADA activity with inhibition constants ranging from 0.012 mM to 0.190 mM. In the in vivo RA model, quercetin significantly reduced joint inflammation and serum CRP levels at a higher dose of 400 mg/kg. Conclusion: Quercetin shows promise as an anti-inflammatory agent for RA by targeting ADA, suggesting that flavonoid-rich plant extracts could enhance RA treatment.

The pyrimidine heterocycle plays an important role in anticancer research. In particular, the pyrimidine derivative families of uracil show promise as structural scaffolds relevant to cervical cancer. This group of chemicals lacks data-driven machine learning quantitative structure-activity relationships (QSARs) that allow for generalization and predictive capabilities in the search for new active compounds. To achieve this, a dataset of pyrimidine and uracil compounds from ChEMBL were collected and curated. A workflow was developed for data-driven machine learning QSAR using an intuitive dataset design and forwards selection of molecular descriptors. The model was thoroughly externally validated against available data. Blind validation was also performed by synthesis and antiproliferative evaluation of new synthesized uracil-based and pyrimidine derivatives. The most active compound among new synthesized derivatives, 2,4,5-trisubstituted pyrimidine was predicted with the QSAR model with differences of 0.02 compared to experimentally tested activity.

Morus alba L. is a plant with a long history of dietary and medicinal uses. We hypothesized that M. alba possesses a significant biological potential. In that sense, we aimed to generate the chemical, antimicrobial, toxicological, and molecular profile of M. alba leaf and fruit extracts. Our results showed that extracts were rich in vitamin C, phenols, and flavonoids, with quercetin and pterostilbene concentrated in the leaf, while fisetin, hesperidin, resveratrol, and luteolin were detected in fruit. Extracts exhibited antimicrobial activity against all tested bacteria, including multidrug-resistant strains. The widest inhibition zones were in Staphylococcus aureus ATCC 33591. The values of the minimum inhibitory concentration ranged from 15.62 μg/ml in Enterococcus faecalis to 500 μg/ml in several bacteria. Minimum bactericidal concentration ranged from 31.25 μg/ml to 1000 μg/ml. Extracts impacted the biofilm formation in a concentration-dependent and species-specific manner. A significant difference in the frequency of nucleoplasmic bridges between the methanolic extract of fruit (0.5 μg/ml, 1 μg/ml, 2 μg/ml), as well as for the frequency of micronuclei between ethanolic extract of leaf (2 μg/ml) and the control group was observed. Molecular docking suggested that hesperidin possesses the highest binding affinity for multidrug efflux transporter AcrB and acyl-PBP2a from MRSA, as well as for the SARS-CoV-2 Mpro. This study, by complementing previous research in this field, gives new insights that could be of great value in obtaining a more comprehensive picture of the Morus alba L. bioactive potential, chemical composition, antimicrobial and toxicological features, as well as molecular profile.

Xanthene derivatives are an important class of heterocyclic compounds with a wide spectrum of pharmacological activities. In our previous investigations, we found the good antiproliferative activity of two xanthene derivatives, with minimal toxicity investigated by in vitro tests. In this study, we tested the interaction of compound 1 (powerful potent antiproliferative compound) with calf thymus DNA (CT-DNA) under physiological conditions by spectrophotometric titration. The probable prediction of binding and the type of interaction forces involved in the arrangement between xanthene derivatives and CT-DNA were explored also through molecular docking studies. The results indicated that compound 1 interacts with CT-DNA by grove binding. The binding constant was found to be 2.5 ∙ 10 4 M −1 indicating the non-covalent binding of compound 1 to CT-DNA. Docking study results proposed possible binding modes, with binding energies of −9.39 and −8.65 kcal mol −1 for compounds 1 and 2, respectively, which supported previously obtained in vitro results for antiproliferative activity. In addition to experimental investigation, density functional theory (DFT) calculation with B3LYP/6-31G*, B3LYP/6-31G**, and B3LYP/6-31+G* levels of theories was performed on compounds 1 and 2 to obtain optimised geometry, spectroscopic and electronic properties. These studies could help in understanding the mechanisms of toxicity, resistance, side effects of xanthene derivatives, and their binding action mechanism to DNA

Two copper(II) complexes of 4-chloro- and 4-dimethylaminobenzaldehyde nicotinic acid hydrazones were prepared and characterized by elemental analysis, mass spectrometry, infrared and electron spectroscopy and conductometry. These rare examples of bis(hydrazonato)copper(II) complexes are neutral complex species with copper(II) center coordinated with two monoanionic bidentate O,N-donor hydrazone ligands coordinated in enol-imine form. The interaction of hydrazone ligands and corresponding copper(II) complexes with CT DNA and BSA was investigated. Copper(II) complexes are slightly effective in binding the DNA than pristine hydrazones. The results indicate groove binding or moderate intercalation which are not significantly affected by the nature of substituent at hydrazone ligands. On contrary, affinities of two copper(II) complexes toward BSA significantly differs and depends on the nature of the substituent, however in absence of thermodynamic data difference in nature of binding forces cannot be excluded. The complex bearing electron-withdrawing 4-chloro substituent has larger affinity toward BSA compared to 4-dimethyamino analogue. These findings were theoretically supported by molecular docking study.