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.

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.