Relationships between the structural characteristic of synthetic chalcones and their antitumoral activity were studied. Treatment of HepG2 cells for 24 h with synthetic 2’-hydroxychalcones resulted in apoptosis induction and dose-dependent inhibition of cell proliferation. The calculated reactivity indexes and the adiabatic electron affinities using the DFT method including solvent effects, suggest a structure-activity relationship between the Chalcones structure and the apoptosis in HepG2 cells. The absence of methoxy substituents in the B ring of synthetic 2’-hydroxychalcones, showed the mayor structure-activity pattern along the series.

Background: Sorafenib is a tyrosine kinase inhibitor (TKI) used to treat hepatocellular carcinoma (HCC), but this drug causes clinically significant toxicities in approximately 50% of patients. Given the high frequency and severity of these side effects, it is necessary to develop new, safer drugs to treat this cancer. Purpose: Novel 2,6,9-trisubstituted pyrimidine derivatives were synthesised and evaluated as potential antitumour agents for HCC. Materials and Methods: Twelve compounds ( 6a–l ) were obtained by a four-step synthetic procedure using a simple and efficient methodology in which two key reactions were promoted by microwave irradiation. Subsequently, compounds 6a–l were evaluated in vitro for cytotoxic activity against the HCC cell line HepG2 and other cell lines; in vivo in the HepG2 xenograft tumour model; and in silico (docking and dynamic simulations). Results and discussion: Compound 6e proved to be the most promising of this series (IC ₅₀ = 5.6 µM), as well as being more index selective than sorafenib and with lower cytotoxicity in Vero cells (18.92 µM). In addition, 6e was further evaluated in Huh-7 cells and demonstrated selectivity for HCC. Docking studies on the proposed targets, VEGFR-2 and B-raf, indicated that 6e could bind to them with binding energies and interaction patterns similar to those of sorafenib. The 6e interaction pattern at the VEGFR-2 binding site was corroborated by dynamic studies over 100 ns. A possible mechanism of 6e -induced HepG2 cell death was investigated. Experiments on caspases-3, -7, -8, -9, Apaf-1, Cyt-c, ERK1/2, and p53 showed that they were all activated, whereas Bcl-2 was inhibited by 6e in HepG2 cells. Furthermore, 6e induced the accumulation of reactive oxygen species (ROS) in HepG2 cells. These results suggest that apoptosis in HepG2 was caused by: (i) a caspase-dependent pathway and (ii) changes in the cellular levels of Bcl-2 family proteins and ROS. In addition, 6e attenuated the growth of HepG2 xenograft tumours in mice at a dose of 1 mg/kg for 3 weeks. Conclusion: Based on these results, this pyrimidine derivative could be an interesting compound for the design of new agents against HCC.

Background: Hepatocellular carcinoma (HCC) is a highly lethal malignancy with limited therapeutic options for advanced disease, motivating the development of metal-based agents that can bypass resistance and improve tumor selectivity. Purpose: This study aimed to evaluate rhenium(I) tricarbonyl complexes bearing 1,10-phenanthroline derivatives, with emphasis on fac -[Re(CO) ₃ (5-chloro-1,10-phenanthroline)Cl] (Re(3)), as potential anti-HCC candidates and to elucidate mechanistic determinants of activity in HepG2 cells. Materials and Methods: Complexes fac -[Re(CO) ₃ (NH ₂ phen)Cl] (Re(1)), fac -[Re(CO) ₃ (NO ₂ phen)Cl] (Re(2)), and Re(3) were synthesized under argon and characterized by ¹ H NMR; electronic structure was examined by DFT (ZORA-PW91/TZP) with COSMO (water), including global reactivity descriptors and frontier orbital composition. Antiproliferative effects were quantified in HepG2 and non-tumor Vero cells using a 72 h resazurin assay (1–150 μM), while apoptosis, caspase activity, oxidative stress, and signaling changes were assessed by Annexin V/7-AAD flow cytometry, Caspase-Glo 3/7, DCFH-DA ROS measurements, western blotting, and immunofluorescence microscopy; statistics used Kruskal–Wallis/Dunn or ANOVA with p < 0.05. Results and Discussion: Re(3) showed pronounced, selective cytotoxicity (IC ₅₀ 6 ± 1.1 μM at 72 h; selective index 5.7; Vero IC ₅₀ > 30 μM), whereas Re(1) and Re(2) were largely inactive (IC ₅₀ > 100 μM). Re(3) induced predominantly apoptotic death (>60% apoptotic cells at 48 h; minimal necrosis), increased caspase-3/7 activity (4–16 h), triggered an early ROS burst (1–20 μM; significant at 2 and 4 h, comparable to CuSO ₄ ), upregulated cytochrome c, caspase-9 and caspase-3, downregulated Bcl-XL, and increased phosphorylated p53, with negligible extrinsic signaling via caspase-8. DFT indicated Re(3) has a stabilized LUMO (−3.34 eV) and electrophilicity (ω = 4.32 eV) with an “optimal” hardness (η = 2.37 eV) supporting sufficient redox reactivity yet kinetic stability; the LUMO localizes (>90%) on the chloro-phenanthroline, consistent with MLCT-driven redox stress. Conclusion: Collectively, Re(3) functions as a tuned redox-active agent, triggering apoptosis through the intrinsic pathway. This process possibly involves mitochondrial modulation with tumor selectivity, supporting its advancement as a lead rhenium-based prototype for HCC and motivating in vivo pharmacology and broader HCC panel validation.

Emerging avian avulaviruses (AVVs) have been identified in Antarctic ecosystems; however, their biological properties and current circulation remain poorly understood. This study utilized historical egg-isolated Antarctic penguin avulavirus strains (AVV17, AVV18, and AVV19) and combined molecular characterization with field surveillance during the 2024–2025 Antarctic season. The historical isolates were molecularly confirmed using RT-qPCR targeting the L gene, confirming their classification as AVV17, AVV18, or AVV19. These isolates were tested for replication indicators in REM 134, MDCK cells and embryonated chicken eggs. Only AVV18 showed evidence of productive replication in REM 134 cells, as indicated by decreasing Ct values and the presence of cytopathic effects.AVV17 and AVV19 were detectable by RT-qPCR but did not exhibit cytopathic changes or replication dynamics. None of the viruses replicated efficiently in MDCK cells. Further propagation of AVV18 in embryonated chicken eggs showed viral amplification in some eggs. Concurrent surveillance at five sites in the South Shetland Islands detected low-level circulation of AVV17–19, exclusively in cloacal swabs, with no viral RNA found in environmental samples. These findings link historical isolates to current circulation, highlighting selective replication among Antarctic AVVs and limited ecological spread in penguin hosts.