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As cancer remains a significant global health challenge, there is an increasing need for novel therapeutic approaches. We investigated the antitumor potential of Juniperus communis berry essential oil on cervical cancer HeLa and colorectal HCT 116 cells. Cytotoxicity was evaluated through the MTT assay, revealing concentration-dependent reductions in cell viability. A clonogenic assay demonstrated long-term cytotoxic effects. Apoptosis markers were assessed via flow cytometric analysis and showed an induction of the intrinsic pathway in both cell lines, demonstrated by the elevated levels of cleaved caspase-3, Bax/Bcl-2 ratio, JC-10 monomer formation, and cytochrome C migration to the cytosol. The treatment inhibited cell-survival pathways in HCT 116 cells and arrested HeLa cells in the S phase. An extensive molecular docking screening provided insight into the binding affinity and interaction patterns of the essential oil components with NADH ubiquinone oxidoreductase and superoxide dismutase enzymes, further confirming the induction of the intrinsic pathway of apoptosis. The obtained in silico and in vitro results indicated the anticancer potential of J. communis berry essential oil as it interferes with cancer cell molecular mechanisms. Our findings highlight J. communis berry essential oil as a promising natural agent with anticancer potential. [ABSTRACT FROM AUTHOR]

Four neutral Rh1–Rh4 complexes of the general formula [Rh2(CH3COO)4L2], where L is an N-alkylimidazole ligand, were synthesized and characterized using various spectroscopic techniques, and in the case of Rh4 the crystal structure was confirmed. Investigation of the interactions of these complexes with HSA by fluorescence spectroscopy revealed that the binding constants Kb are moderately strong (∼104 M−1), and site-marker competition experiments showed that the complexes bind to Heme site III (subdomain IB). Competitive binding studies for CT DNA using EB and HOE showed that the complexes bind to the minor groove, which was also confirmed by viscosity experiments. Molecular docking confirmed the experimental data for HSA and CT DNA. Antimicrobial tests showed that the Rh2–Rh4 complexes exerted a strong inhibitory effect on G+ bacteria B. cereus and G− bacteria V. parahaemolyticus as well as on the yeast C. tropicalis, which showed a higher sensitivity compared to fluconazole. The cytotoxic activity of Rh1–Rh4 complexes tested on three cancer cell lines (HeLa, HCT116 and MDA-MB-231) and on healthy MRC-5 cells showed that all investigated complexes elicited more efficient cytotoxicity on all tested tumor cells than on control cells. Investigation of the mechanism of action revealed that the Rh1–Rh4 complexes inhibit cell proliferation via different mechanisms of action, namely apoptosis (increase in expression of the pro-apoptotic Bax protein and caspase-3 protein in HeLa and HCT116 cells; changes in mitochondrial potential and mitochondrial damage; release of cytochrome c from the mitochondria; cell cycle arrest in G2/M phase in both HeLa and HCT116 cells together with a decrease in the expression of cyclin A and cyclin B) and autophagy (reduction in the expression of the protein p62 in HeLa and HCT116 cells). [ABSTRACT FROM AUTHOR]

A serie of novel square pyramidal copper(ii) complexes [Cu(L)2H2O] (3a–d) with O,O-bidentate ligands [L = ethyl-2-hydroxy-4-aryl-4-oxo-2-butenoate; aryl = 3-methoxyphenyl-2a, (E)-2-phenylvinyl-2b, (E)-2-(4′-hydroxy-3′-methoxyphenyl)vinyl-2c, 3-nitrophenyl-2d, 2-thienyl-2e] were synthesized and characterized by spectral (UV-Vis, IR, ESI-MS and EPR), elemental and X-ray analysis. The antimicrobial activity was estimated by the determination of the minimal inhibitory concentration (MIC) using the broth microdilution method. The most active antibacterial compounds were 3c and 3d, while the best antifungal activity was showed by complexes 3b and 3e. The lowest MIC value (0.048 mg mL−1) was measured for 3c against Proteus mirabilis. The cytotoxic activity was tested using the MTT method on human epithelial carcinoma HeLa cells, human lung carcinoma A549 cells and human colon carcinoma LS174 cells. All complexes showed extremely better cytotoxic activity compared to cisplatin at all tested concentrations. Compound 3d expressed the best activity against all tested cell lines with IC50 values ranging from 7.45 to 7.91 μg mL−1. The type of cell death and the impact on the cell cycle for 3d and 3e were evaluated by flow cytometry. Both compounds induced apoptosis and S phase cell cycle arrest. The interactions between selected complexes (3d and 3e) and CT-DNA or bovine serum albumin (BSA) were investigated by the fluorescence spectroscopic method. Competitive experiments with ethidium bromide (EB) indicated that 3d and 3e have a propensity to displace EB from the EB–DNA complex through intercalation suggesting strong competition with EB [Ksv = (1.4 ± 0.2) and (2.9 ± 0.1) × 104 M−1, respectively]. Ksv values indicate that these complexes bind to DNA covalently and non-covalently. The achieved results in the fluorescence titration of BSA with 3d and 3e [Ka = (2.9 ± 0.2) × 106 and (2.5 ± 0.2) × 105 M, respectively] showed that the fluorescence quenching of BSA is a result of the formation of the 3d– and 3e–BSA complexes. The obtained Ka values are high enough to ensure that a significant amount of 3d and 3e gets transported and distributed through the cells. [ABSTRACT FROM AUTHOR]

• Synthesis and cytotoxic properties of novel 3-hydroxy-3-pyrrolin-2-ones bearing thenoyl fragment. • Compounds D10 , D13 , D14 , and D15 showed highest cytotoxicity against malignant cells. • Mechanisms of cytotoxic activity suggested that D13 , D15 , and D10 in HeLa cells induce apoptosis that is associated with S phase arrest. • D13 and D15 have great affinity to displace EB from the EB-DNA complex through intercalation. In order to make a progress in discovering a new agents for chemotherapy with improved properties and bearing in mind the fact that substituted 3-hydroxy-3-pyrrolin-2-ones belong to a class of biologically active compounds, series of novel 1,5-diaryl-4-(2-thienylcarbonyl)-3-hydroxy-3-pyrrolin-2-ones were synthesized and characterized by spectral (UV–Vis, IR, NMR, ESI-MS), X-ray and elemental analysis. All compounds were examined for their cytotoxic effect on human cancer cell lines HeLa and MDA-MB 231 and normal fibroblasts (MRC-5). Four compounds, 3-hydroxy-1-(p-tolyl)-4-(2-thienylcarbonyl)-5-(4-chlorophenyl)-2,5-dihydro-1H-pyrrol-2-one (D10), 3-hydroxy-1-(3-nitrophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D13), 3-hydroxy-1-(4-nitrophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D14), and 3-hydroxy-1-(4-chlorophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D15), that showed the highest cytotoxicity against malignant cells and the best selectivity towards normal cells were selected for further experiments. Results obtained by investigating mechanisms of cytotoxic activity suggest that selected 3-hydroxy-3-pyrrolin-2-one derivatives in HeLa cells induce apoptosis that is associated with S phase arrest (D13 , D15 , and D10) or unrelated to cell cycle distribution (D14). Additionally, to better understand their suitability for potential use as anticancer medicaments we studied the interactions between biomacromolecules (DNA or BSA) and D13 and D15. The results indicated that D13 and D15 have great affinity to displace EB from the EB-DNA complex through intercalation [K sv = (3.7 ± 0.1) and (3.4 ± 0.1) × 103 M−1, respectively], an intercalative mode also confirmed through viscosity measurements. K a values, obtained as result of fluorescence titration of BSA with D13 and D15 [K a = (4.2 ± 0.2) and (2.6 ± 0.2) × 105 M, respectively], support the fact that a significant amount of the tested compounds could be transported and distributed through the cells. In addition, by DNA and BSA molecular docking study for D13, D14 and D15 is determined and predicted the binding mode and the interaction region. [ABSTRACT FROM AUTHOR]