New series of thiazolyl-pyrazoline derivatives (7a–7d, 10a–10d and 13a–13f) have been synthesised and assessed for their potential EGFR and VEGFR-2 inhibitory activities. Compounds 10b and 10d exerted potent and selective inhibitory activity towards the two receptor tyrosine kinases; EGFR (IC₅₀ = 40.7 ± 1.0 and 32.5 ± 2.2 nM, respectively) and VEGFR-2 (IC₅₀ = 78.4 ± 1.5 and 43.0 ± 2.4 nM, respectively). The best anti-proliferative activity for the examined thiazolyl-pyrazolines was observed against the non-small lung cancer cells (NSCLC). Compounds 10b and 10d displayed pronounced efficacy against A549 (IC₅₀ = 4.2 and 2.9 µM, respectively) and H441 cell lines (IC₅₀ = 4.8 and 3.8 µM, respectively). Moreover, our results indicated that 10b and 10d were much more effective towards EGFR-mutated NSCLC cell lines (NCI-H1650 and NCI-H1975 cells) than gefitinib. Finally, compounds 10b and 10d induce G2/M cell cycle arrest and apoptosis and inhibit migration in A549 cancerous cells. Graphical Abstract

In this study, we aimed to develop hybrid antitumor compounds by synthesizing and characterizing novel N-substituted acrididine-1,8-dione derivatives, designed as hybrids of phthalimide and acridine-1,8-diones. We employed a three-step synthetic strategy and characterized all compounds using IR, ¹H NMR, ¹³C NMR, and LC–MS. The cytotoxicity and antitumor activity of five compounds (8c, 8f, 8h, 8i, and 8L) against four cancer cell lines (H460, A431, A549, and MDA-MB-231) compared to human skin fibroblast cells were evaluated. Among the synthesized compounds, compound 8f showed promising activity against skin and lung cancers, with favorable IC₅₀ values and selectivity index. The relative changes in mRNA expression levels of four key genes (p53, TOP2B, p38, and EGFR) in A431 cells treated with the five synthesized compounds (8c, 8f, 8h, 8i, and 8L) were also investigated. Additionally, molecular docking studies revealed that compound 8f exhibited high binding affinity with TOP2B, p38, p53, and EGFR, suggesting its potential as a targeted anticancer therapy. The results obtained indicate that N-substituted acrididine-1,8-dione derivatives have the potential to be developed as novel antitumor agents with a dual mechanism of action, and compound 8f is a promising candidate for further investigation.

The present study aimed to test the anti-inflammatory and xanthine oxidase inhibitory activities of two synthesized molecules and compare them to routinely prescribed nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac and the serum urate-lowering drug, allopurinol. The anti-inflammatory effects of the designed compounds (A and B) were evaluated in carrageenan (CAR)-induced paw edema in mice. The levels of nitric oxide and myeloperoxidase activity were measured in paw skin using biochemical methods. Additionally, prostaglandin E2 (PGE2), C-reactive protein (CRP), cyclooxygenase-2 (Cox-2), tumor necrosis factor-α (TNFα), interleukin (IL)-1β, IL-2 and IL-10, and monocyte chemoattractant protein-1 (MCP1) were assessed by enzyme-linked immunosorbent assay (ELISA). The expression of inflammation-related genes was confirmed by real-time qPCR. The expression of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB) were estimated using immunohistochemistry, and xanthine oxidase inhibitory activity was evaluated using an in vitro assay. The results revealed that compounds A and B decreased inflammation, as was observed by a reduction in the elevation of all the tested markers. In addition, the tested compounds markedly decreased paw swelling, mobilization of inflammatory cells, iNOS-, and NF-κB-immunoreactive cells in a mouse model of paw edema. Interestingly, both compounds were potent xanthine oxidase inhibitors as well as Cox inhibitors with higher activity in favor of compound B providing potential dual acting series of anti-hyperuricemic and anti-inflammatory therapeutic agents.

A novel folic acid-conjugated, iron-based MOF (MIL-101(Fe)) loaded with 1,8-acridinediones (DO8) was developed for targeted photodynamic therapy (PDT) of HepG-2 cells. This composite aims to trigger an anticancer response through sequential PDT and chemotherapy. The nanocomposite exhibited high stability in a physiological environment with a pH of 7.4. It was also able to release DO8 continuously in an acidic environment with a pH of 5, which shows that it can adapt to the conditions in the tumor microenvironment. The MIL-101(Fe)MOF-FA@DO8 nanoparticles (NPs) with 30% and 50% DO8 have been studied in vitro under different conditions (light and dark) and have been shown to be compatible with living tissues and specifically target HepG-2 cells. The IC₅₀ values of 50% DO8 and 30% DO8 loaded MOF-FA were found to be 88.67 and 105.9 μg mL⁻¹ under dark conditions, respectively. Under light conditions, they demonstrated the highest efficacy in inhibiting tumor cell growth. The IC₅₀ values were found to be 8.94 and 11.78 μg mL⁻¹. Flow cytometry analysis of annexin V/PI-stained apoptotic and necrotic cells in HepG-2 cells treated with the modified MIL-101-FA@50% DO8 NPs at IC₅₀ doses under both dark and light conditions indicates that the primary mechanism of cell death is necrosis, likely due to the enhanced formation of reactive oxygen species (ROS) under light conditions compared to that under dark conditions. This increased reactive oxygen species (ROS) generation leads to extensive membrane rupture, resulting in significant cell damage after treatment with the modified MIL-101-FA@50% DO8 NPs. These findings underscore the potential of this nanocomposite as an effective PDT agent for targeted cancer therapy.

In the racemic title compound, C₂₃H₂₀N₂O₄S, the sulfur atom is attached equatorially to the sugar ring with unequal S—C bonds, viz.: S—C_s = 1.808 (2) and S—C_p = 1.770 (2) Å (s = sugar, p = pyridyl). The dihedral angles between the pyridine ring and its attached phenyl groups are 42.24 (8) and 6.37 (14)°. In the crystal, a system of classical O—H...O and O—H...(O,O) hydrogen bonds links the molecules to form tube-like assemblies propagating parallel to the c-axis direction. Weak C—H...N interactions are also observed.