Anna Bielawska

Background: The development of novel tubulin-targeting agents remains a promising strategy in anticancer drug design. In the present study, novel heterocyclic tubulin-targeting compounds were identified using a complex in silico/in vitro workflow. Methods: An in-house library of approximately 8000 structurally diverse heterocyclic compounds was screened for antiproliferative activity, yielding 260 experimentally validated hits. These compounds were docked against the colchicine, vinca, and taxane binding sites of tubulin. Selected compounds were also tested for their effects on cellular β-tubulin protein levels in Jurkat cells. Results: Docking analysis indicated that 42 compounds matched or exceeded colchicine’s binding energy, 3 compounds were comparable to vinblastine, and 18 compounds surpassed paclitaxel, suggesting the colchicine and taxane sites as preferred targets. Five top-scoring compounds (Les-6370, Les-4272, Les-4309, Les-4403, and Les-1419) were further analyzed via molecular dynamics simulations, confirming stable binding—particularly at the colchicine site—and favorable hydrogen-bonding and lipophilic interactions. At 10 µM, Les-1419 and Les-4309 reduced total cellular β-tubulin protein levels in Jurkat cells by 57.73% and 54.31%, respectively, relative to the effect observed for the reference compound Combretastatin A-4. Conclusions: This study resulted in the identification of novel starting scaffolds with favorable tubulin interaction activity and predicted drug-like properties, representing structurally novel parent structures and serving as promising starting points for further structural optimization and analogue development.

4-Thiazolidinone derivatives, a group of compounds with a broad spectrum of activity and anticancer properties, are used in medicine as anti-inflammatory, antiviral, antibacterial, antidiabetic, and blood pressure-lowering drugs; some of them are now in phase II and III clinical trials as anticancer drugs. Here, we evaluated the anticancer potential of 4-thiazolidinones (2b, 12b, 14b) targeting tubulin and metastasis-related pathways in breast cancer models. Molecular docking revealed that compound 14b exhibited the strongest binding affinity to the paclitaxel-binding site of β-tubulin, outperforming 2b and 12b, though slightly weaker than Taxol. Biological assays confirmed significant tubulin inhibition, with 14b reducing β-tubulin levels up to eight-fold in MCF-7 cells and two-fold in MDA-MB-231 cells. All compounds promoted tubulin polymerization, showing paclitaxel-like activity, with comparable the maximum velocity (V_max) values. Cell cycle analysis demonstrated G2/M arrest in MCF-7 cells and S-phase accumulation in MDA-MB-231 cells. Overall, compound 14b demonstrated the most promising multitarget anticancer activity in vitro.

Despite increasing awareness about cancer, it still remains one of the biggest threats to human life. Breast cancer is among the most commonly diagnosed types of cancer. Pentacyclic triterpenoids are a group of plant compounds commonly known in traditional medicine due to their anti-inflammatory, antibacterial, antidiabetic, cardioprotective and anticancer effects. This review examined the potential of pentacyclic triterpenoid acids in the treatment of breast cancer, focusing on research from the past 15 years. Although the subject literature demonstrates that pentacyclic acids show anticancer activity, it also reveals their limitations such as low bioavailability, aqueous solubility, or high IC₅₀ values. Therefore, to overcome these limitations, structural modifications, mostly at the C3 and C28 positions, were made, and several novel derivatives with oleanane, lupane and ursane skeletal types were synthesized. This review not only identified pentacyclic acids derivatives but also evaluated how structural modifications enhanced their biological activity and potential in breast cancer treatment. The findings revealed that even though the obtained derivatives enhanced anticancer potential against breast cancer, the main issues of bioavailability and solubility remain unsolved, suggesting that future research in synthesis should focus not only on improving cytotoxicity but also on the bioavailability of novel compounds.

Wood-inhabiting fungi constitute a valuable source of biologically active compounds with significant therapeutic potential. Particular attention is paid to species known for their high content of polysaccharides, triterpenoids, phenolic compounds, and other secondary metabolites exhibiting cytotoxic and immunomodulatory activities. The results indicate that extracts obtained from these fungi may inhibit tumor growth, induce apoptosis, and support the immune response of the organism. Although further clinical studies are required, wood-inhabiting medicinal fungi represent a promising direction in the development of natural anticancer therapies and complementary treatment strategies.

With global cancer cases projected to reach 35 million by 2050 and drug resistance to existing chemotherapeutic drugs remaining a significant threat in cancer therapy, accounting for up to 90% of chemotherapy failures, the search for novel anticancer compounds continues to be increasingly important. This systematic review (2021–2025) examined the role of thiazoles and 4-thiazolidinones/thiazolidinediones as popular scaffolds in existing anticancer drug design. While researchers continue to focus on well-established molecular targets, such as EGFR, VEGFR-2, and tubulin, there is a notable difference regarding other preferred choices for thiazoles and 4-thiazolidinones/thiazolidinediones. Among analyzed mechanisms of anticancer activity notably favored for thiazoles was the inhibition of serine/threonine protein kinases (CDK-2, BRAF^V600E), while for 4-thiazolidinones/thiazolidinediones more studied were ROS generation and PPARγ activation. Furthermore, less-researched mechanisms of anticancer activity with no FDA-approved drugs such as PTP1B, SIRT2, PKM2, eIF4E, CA XI and XII inhibition for thiazole derivatives and pan-PIM kinase and BAG3 protein inhibition for 4-thiazolidinones/thiazolidinediones were evaluated as well. Notable was the popularity of the multi-targeting approach for modern drug design, with ~30% reporting two or more targets for their compounds. Despite these advancements, the review identified critical gaps in ADMET evaluations, safety analyzing against normal human cells and the lack of mechanistic studies connecting the targeted protein and the compounds anticancer effects.

Background/Objectives: Adipokines and cytokines, secreted by adipocytes and immune cells, play key roles in metabolic and inflammatory processes. This study aimed to assess the association between salivary visfatin levels and metabolic dysfunction-associated steatotic liver disease (MASLD), determine a salivary visfatin cutoff associated with increased risk of this disease, and examine correlations among selected adipokines, cytokines, and gelatinases in serum and saliva of obese patients. Methods: The study included 65 participants (40 women and 25 men) with a body mass index (BMI) ranging from 30.0 to 39.9 kg/m², who were divided into groups based on whether the salivary visfatin concentration exceeded the quantification limit (1.229 ng/mL). Body composition analysis was performed using the bioelectrical impedance method, quantitative assessment of hepatic steatosis was carried out using transient elastography, and the concentrations of selected adipokines, cytokines, and gelatinases were determined in serum and saliva. Results: A relationship was observed between lower BMI and salivary visfatin concentrations below the quantification limit (p = 0.017), and between the absence of MASLD and visfatin levels below the quantification threshold in saliva (p = 0.05). Higher concentrations of interleukin-1β (p = 0.003) and matrix metalloproteinase-2 (p = 0.019) in saliva, as well as interleukin-6 (p = 0.002) in serum, were observed in the group with salivary visfatin levels above the quantification limit. Correlations were found between salivary and serum IL-6 concentrations (r = 0.30; p = 0.016) and between serum resistin and salivary IL-6 levels (r = 0.24; p = 0.056), as well as between serum IL-6 and salivary MMP-2 concentrations (r = 0.24; p = 0.059). Conclusions: In this pilot study, salivary visfatin levels were found to differ between obese individuals with and without MASLD and to be associated with selected anthropometric parameters and inflammatory markers, but the observed associations are exploratory and require confirmation.

Oxidative stress, inflammation, and environmental factors contribute significantly to the development of ocular disorders, including dry eye disease, conjunctivitis, and age-related degenerative changes. In recent years, growing attention has been directed toward natural compounds and plant-derived extracts with potential protective and therapeutic effects on eye health. This work provides an overview of selected bioactive substances, such as carotenoids (β-carotene), flavonoids, vitamins C and E, and phytochemicals derived from plants. These agents exhibit antioxidative, anti-inflammatory, antimicrobial, and regenerative properties that may support ocular surface integrity, reduce oxidative damage, and improve visual performance. The integration of such natural remedies into ocular health strategies may offer complementary benefits to conventional therapies.

Background/Objectives: Cancer persists as a leading concern in the current medical field. As such, scientists are continuously researching new compounds with anticancer potential. In this study, we explored fifteen new 4-thiazolidinone derivatives as potential anticancer compounds. 4-Thiazolidinones are a well-established group of active structures, most commonly applied for the treatment of Parkinson’s disease and diabetic neuropathy. However, they are actively researched as potential anticancer agents. A number of derivatives have qualified for Phase II and III clinical trials as antitumor agents. Methods: MTT cytotoxicity assay was applied to identify the most active compounds. Three out of the fifteen tested structures displayed a significant inhibitory effect on the MCF-7 and MDA-MB-231 cell lines. To further investigate the influence of compounds on breast cancer cells, we analyzed their capability to induce apoptosis using flow cytometry assessment with Annexin V and propidium iodide dyes. Next, flow cytometry analysis of JC-1 dye was utilized to research their capability to affect mitochondrial membrane. Afterwards, concentrations of important proapoptotic proteins such as Bax and cytochrome C were assessed with a highly sensitive ELISA method. Results: Further analysis with a fluorescent microscope displayed that novel compounds significantly increase the generation of reactive oxygen species. Conclusions: The results represented in this article displayed that the most active compounds positively affected the activation of the intrinsic apoptotic pathway in the tested breast cancer cells.

As breast cancer remains a significant challenge for the current medical field, molecules with a 4-thiazolidinone scaffold can become promising candidates for addressing the increasing threat of cancer. This study aims to develop and evaluate the novel 4-thiazolidinone derivatives with anticancer potential. New compounds were synthesized through two different pathways, one as a two-step process and the other as a one-pot method. The second approach fits the requirements of cost-effective methodologies and allows for the reduction of synthetic steps, reagents, and reaction time. The obtained data from in vitro research showed a potent cytotoxic activity of the novel structures in micromolar concentrations against MCF-7 breast cancer cells. Further investigations into their anticancer activity revealed that the tested compounds induced apoptosis through intrinsic and extrinsic pathways, which was evidenced by their capability to reduce the mitochondrial membrane potential and induce the activation of caspases 7, 8, 9, and 10. A more detailed analysis uncovered that one of the novel compounds can affect the expression of key apoptotic proteins, tumor protein P53 (p53), cytochrome C, and Bax in treated cells. Additionally, these compounds displayed an enhanced generation of reactive oxygen species (ROS) in MCF-7 cells, which suggests that ROS-mediated mechanisms can take part in the anticancer potential of the synthesized compounds.

Colorectal cancer is a major global health challenge, with current treatments limited by toxicity and resistance. Thiazole derivatives, known for their bioactivity, are emerging as promising alternatives. Juglone (5-hydroxy-1,4-naphthoquinone) is a naturally occurring compound with known anticancer properties, and its incorporation into thiopyrano[2,3-d]thiazole scaffolds may enhance their therapeutic potential. This study examined the cytotoxicity of thiopyrano[2,3-d]thiazoles and their effects on apoptosis in colorectal cancer cells. Les-6547 and Les-6557 increased the population of ROS-positive HT-29 cancer cells approximately 10-fold compared with control cells (36.3% and 38.5% vs. 3.8%, respectively), potentially contributing to various downstream effects. Elevated ROS levels were associated with cell cycle arrest, inhibition of DNA biosynthesis, and reduced cell proliferation. A significant shift in the cell cycle distribution was observed, with an increase in S-phase (from 17.3% in the control to 34.7% to 51.3% for Les-6547 and Les-6557, respectively) and G2/M phase (from 24.3% to 39.9% and 28.8%). Additionally, Les-6547 and Les-6557 inhibited DNA biosynthesis in HT-29 cells, with IC₅₀ values of 2.21 µM and 2.91 µM, respectively. Additionally, ROS generation may initiate the intrinsic apoptotic pathway. Les-6547 and Les-6557 activated both intrinsic and extrinsic apoptotic pathways, demonstrated by notable increases in the activity of caspase 3/7, 8, 9, and 10. This study provides a robust basis for investigating the detailed molecular mechanisms of action and therapeutic potential of Les-6547 and Les-6557.