Zinc pyrithione is an organometallic compound with antimicrobial activity used in many industrial products. In this study, cytotoxicity (cell viability, lactate dehydrogenase release, proliferation rate, and mitotic index) and genotoxicity (sister chromatid exchange and micronucleus test) of zinc pyrithione on human lymphocytes were determined. Intracellular zinc concentrations were determined by inductively coupled plasma-optical emission spectrometry. Intracellular antioxidant/oxidant status was evaluated by total antioxidant capacity and total oxidative status assays. Its irritation potential was investigated using the hen’s egg test chorioallantoic membrane model. Up to the highest concentration of 1000 nmol/L, ZnPT did not cause genotoxicity and did not change the proliferation index. Above 500 nmol/L, zinc pyrithione caused an increase in lactate dehydrogenase, oxidative stress, and intracellular zinc levels, while decreasing cell viability and mitotic index level. At 1000 nmol/L, zinc pyrithione caused slight irritation. These results suggest that zinc pyrithione may exert toxic effects via increased oxidative stress on human cellular systems.

Background/Objectives: Cancer is among the leading causes of mortality worldwide. In 2022 alone, the global cancer death toll stood at 9.74 million. Projections indicate that this figure will rise to 10.4 million by 2025. Methods: A new series of benzimidazolone-bridged hybrid compounds containing thiophene, furan, oxadiazole, piperazine, and coumarin moieties was synthesized and structurally characterized by ¹H-NMR, ¹³C-NMR (APT), and elemental analysis. Their cytotoxic effects were evaluated by MTT assay against human lung (A549), human breast (MCF-7), and human cervical (HeLa) cancer cell lines, and the non-cancerous HEK293 cell line after 48 h exposure over a concentration range of 0.5–250 µM. IC₅₀ values were determined, and Selectivity Indexes (SI) were calculated using HEK293 as the reference normal cell line. Molecular docking studies were carried out using the Glide XP protocol against VEGFR2 (PDB ID: 4ASD) and CDK4–Cyclin D3 (PDB ID: 7SJ3), with sorafenib and abemaciclib as reference inhibitors. Results: The results of anticancer activity were compared with doxorubicin (IC₅₀ ± SD (µM)/SI: 4.3 ± 0.2/1.20 for A549, 6.4 ± 0.37/0.77 for MCF-7, 3.4 ± 0.19/1.54 for HeLa), a drug used for cancer chemotherapy. The structures of the newly synthesized hybrid compounds were identified by ¹H-NMR, ¹³C-NMR (APT), and elemental analysis data. These hybrid compounds represent a promising class of anticancer agents. Several compounds demonstrated marked and concentration-dependent cytotoxicity across all cancer cell lines, with HeLa cells showing the highest overall sensitivity. The introduction of an oxadiazole ring (compound 7) and coumarin substituents (compounds 12b–12d) markedly improved anticancer activity and selectivity, yielding low-micromolar IC₅₀ values in HeLa cells (10.6–13.6 µM) and high Selectivity Indexes (SI = 2.0–3.63). Compound 6 also exhibited balanced potency across A549, MCF-7, and HeLa cells (IC₅₀ = 28.3–31.2 µM) with SI values ≥ 2.0. Compound 9 showed strong cytotoxicity across all cancer cell lines; its moderate SI values indicate lower discrimination between malignant and non-malignant cells. Taken together, these findings identified compounds 7, 12b–12d, 6, and 12c as the most promising benzimidazolone-based candidates, displaying both potent cytotoxicity and favorable selectivity over non-malignant HEK293 cells. Conclusions: Among the synthesized molecules, the oxadiazole derivative (7) and the coumarin-based hybrids (12b–12d) exhibited the strongest combination of cytotoxic activity and selectivity, reflected by their low IC₅₀ values and high SI ratios. Notably, compound 12c combined strong biological activity with the highest predicted VEGFR2 affinity in the series, highlighting it as a particularly promising scaffold. While compound 9 exhibited excellent docking scores toward both VEGFR2 and CDK4, its lower selectivity suggests a need for further structural refinement. Overall, the biological and computational findings converge to identify these benzimidazolone hybrids as credible lead candidates for future anticancer optimization.

This study was conducted to evaluate antioxidant, antimutagenic and antimicrobial activities as well as irritation/toxicity efficacy of n-hexane, chloroform and methanol extracts of the red algae Ceramium rubrum C. Agardh (1881). While spectrophotometric methods were used for the determination of total phenol and flavonoid content, antioxidant activity was evaluated by DPPH assay. Antimicrobial and antimutagenic efficacy of extracts were determined by MIC method and Ames test, respectively. Also, HET-CAM test was used for irritation/toxicity of extracts. While methanol extract was found to have higher total flavonoid and phenolic contents than the other extracts and hexane showed higher antioxidant activity than other extracts. All extracts exerted moderate antimicrobial activity against tested microorganisms as 64–256 μg/mL. However, extracts of the algae did not show any mutagenicity or irritation effect even at the highest concentration.