Protoporphyrin IX is a natural photosensitizer used in photodynamic therapy. In this work, we present the synthesis, physicochemical characterisation, and photophysical studies of pegylated derivatives of protoporphyrin IX, two of which exhibit nanomolar activity against the A2780 and SK-Mel-28 cell lines. The most active compound exhibits IC50 values of 15.7 ± 3.4 nM for A2780 and 25.1 ± 14.3 nM for SK-Mel-28 following exposure to a light fluence of 5 J/cm2. The length of the PEG chain and the chemical group at its end both affected the observed biological activity. It was noted that the ethyl-ended polyethylene glycol chain of protoporphyrin IX influenced activity significantly less in comparison to the methyl-ended chain in the same study.

Herein, we report a novel series of heterocyclic fluoro-methoxy-phenyl-substituted N-sulfonylpiperidine mono-spiro-1,2,4,5-tetraoxanes (5a-l; 50-93%) that have been successfully synthesised under metal-free and environmentally benign conditions. The inhibitory effects of all derivatives (5a-l) were determined in vitro on Plasmodium falciparum, Trypanosoma brucei, Mycobacterium, HeLa, and A2780 ovarian cancer cell cultures. The heterocyclic 1,2,4,5-tetraoxanes (5a-l; IC50 = 4.1-16.2 μM) displayed interesting micromolar antiplasmodial potential against chloroquine-resistant FcB1 strains of P. falciparum. Moreover, four representative analogues (5e, 5h, 5k, 5b) were evaluated in Danio rerio larvae, showing no lethality within the tested range, with sublethal morphological alterations observed at higher concentrations. As a result of a complex biological activity assessment, compounds with micromolar antiparasitic and antimycobacterial activities were identified, within an acceptable cytotoxicity range. Notably, the presented study constitutes the first evidence of a non-steroidal monomeric p-OCF3-Ph-based 2-fluoro-p-OMe-phenyl ring-substituted N-sulfonylpiperidine mono-spiro-1,2,4,5-tetraoxane (5j; Pf FcB1 IC50 = 5.5 μM, Tbb IC50 = 25.6 μM, M. tuberculosis H37Ra MIC50 = 40 μM) exhibiting efficient multispecies-targeting susceptibilities.

Complexes of colchicine, colchiceine, and 10-methylthiocolchicine with Li+, Na+, and K+ cations in the form of chlorides were synthesized and then subjected to spectral analysis, DFT theoretical studies, and molecular modeling. The values for water solubility and lipophilicity were also determined using various platforms; both factors are very important for determining the bioavailability of the tested compounds. These compounds were also tested for their fungicidal, herbicidal, insecticidal, and cytotoxic activities. Preliminary in silico studies showed that colchicine, colchiceine, 10-methylthio-colchicine, and their chloride complexes are inactive against selected fungi, weeds, and insects. Colchicine did not show antifungal properties in biological tests and was only active against Aureobasidium pullulans, as were its chloride complexes. The process of complexing colchiceine with metal cations in chloride salts significantly improved the antifungal potency against the selected species A. pullulans and Chaetomium globosum. The highest efficacy of colchiceine complexes was observed only against A. pullulans (MIC = 130 µg/mL) and Ch. globosum (MIC = 65 μg/mL). In contrast to the antifungal activity results, anticancer studies showed that 10-methylthiocolchicine complexes are more active against the SKOV-3 cell line (~IC50 = 2 nM) than colchicine or colchiceine. Molecular-modeling studies confirmed that lithium-coordinated compounds strongly stabilized the active ligand-tubulin complex, which may contribute to the observed cytotoxic activity.

This study presents the synthesis, physicochemical characterisation, and biological evaluation of a series of novel pyrrole-substituted flavone derivatives with potential therapeutic applications. Phenylated and halogenated pyrrole derivatives of flavones were obtained via Paal-Knorr condensation of 6- and 7-aminoflavones with various 1,4-diketones and their subsequent halogenation. The physicochemical properties and chemical structures of the novel compounds were confirmed using UV-VIS and NMR spectroscopy, mass spectrometry, X-ray diffraction and thermal analyses. Crystallographic studies revealed distinct packing motifs, with halogenated derivatives demonstrating recurring structural patterns and isostructurality, suggesting a crucial role of halogen bonding in crystal organisation. A combination of X-ray powder diffraction and thermal analyses confirmed the purity and stability of the compounds. Biological screening against Plasmodium falciparum identified 2-phenyl-7-(2,3,5-triphenylpyrrol-1-yl)chromen-4-one as the most potent antiplasmodial agent with the IC50 value of 1.37 mu g/ml, whereas moderate activity was noted for 2-phenyl-6-(2,3,5-triphenylpyrrol-1-yl)chromen-4-one and other analogues. Preliminary cytotoxicity assays on the human bladder cancer 5637 cell line revealed that halogen substitution at position 6 of the flavone scaffold, particularly in 6-(3,4-diiodo-2,5-dimethyl-pyrrol-1-yl)-2-phenyl-chromen-4-one, significantly increased cytotoxic potential (IC50 < 5 M), albeit with limited selectivity toward non-cancerous cells. Overall, these findings highlight the importance of structural modifications in influencing biological activity and suggest that selected pyrrole-flavone derivatives, especially 2-phenyl-7-(2,3,5-triphenylpyrrol-1-yl)chromen-4-one and 6-(3,4-diiodo-2,5-dimethyl-pyrrol-1-yl)-2-phenyl-chromen-4-one, may serve as promising scaffolds for further optimisation as antiparasitic and anticancer agents.

Abstract A highly efficient metal and catalyst-free approach for the preparation of synthetically challenged tri -OMe-aryl-substituted heterocyclic, di -/ tri -OMe-aryl-based cyclic and acyclic 1,2,4,5-tetraoxanes ( 5a–l and 6a–k ) is presented herein. Under green-chemistry conditions, the reactions occur in two key steps. The first one involves azeotropic activation of hydrogen peroxide for N -sulfonylpiperidone ( 2a–f ), substituted cyclic and acyclic ketones ( 2a 1 –a 4 ) oxidation, whereas the second one was H + [BF 4 ]ˉ (50–55% solun; 25 mol%)-catalyzed cyclization of the highly reactive gem -dihydroperoxide ( 3a–f and 3a 1 –a 4 ) intermediates in an SN 1 -type manner with secondary keto compounds ( 4a–d ). Both reactions furnished a diverse array of heterocyclic, cyclic, and open-chain 1,2,4,5-tetraoxane analogues ( 5a–l and 6a–k ; 19–83%) in attainable yields. The outcomes of the control and competition experiment strongly indicate that the electronic effects of the EWGs group and the strong steric influence of the bulky tri -OMe-aryl group directly impacted reaction advancement. These effects were clearly observed in the reactivity of the substituted N -sulfonylpiperidones ( 2a–f ) and gem -dihydroperoxides ( 3a–f and 3a 1 –a 4 ), and finally, also in the construction of the final products ( 5a–l and 6a–k ). In addition, this metal-free approach is also suitable for the ‘one pot’ synthesis of structurally complex, highly substituted, pharmaceutically privileged di -/ tri -OMe-aryl-based cyclic and acyclic 1,2,4,5-tetraoxanes ( 6a–h and 6k ), offering significant potential for synthetic advancements in malaria and cancer chemotherapy. Furthermore, in preliminary biological evaluations, the in vitro antiplasmodial and cytotoxic potentials of novel tri -OMe-aryl-substituted N -sulfonylpiperidine-spiro-1,2,4,5-tetraoxanes ( 5a–l ) were established against the chloroquine-resistant FcB1 strain of Plasmodium falciparum and human cancer cell lines, including HeLa and A2780 cells.

Curcumin is a well-known compound with anticancer properties, as demonstrated in preclinical studies. However, its clinical potential is limited by several drawbacks. Medicinal chemistry, therefore, offers the opportunity to develop curcumin derivatives through structural modifications. This study showed cytotoxic activity of curcumin derivatives in muscle-invasive bladder cancer cells (HT-1376). Cytotoxicity was assessed under normoxic and hypoxic conditions and compared with effects on human primary bladder epithelial cells (BdEC). The most promising compounds (2a and 2a-B) were further investigated in a 3D cell culture model. Mechanistic studies included the evaluation of lactate dehydrogenase release, cell cycle distribution, and induction of apoptosis and necrosis using luminescent-, colorimetric-, and fluorescence-based assays. Furthermore, the intracellular uptake was investigated using flow cytometry and confocal microscopy. Tested compounds showed greater cytotoxicity than curcumin, with enhanced effects under hypoxic conditions. The derivatives containing a keto-enol moiety showed greater selectivity for bladder cancer cells than curcumin. Compounds 2a and 2a-B also showed greater cytotoxicity in the 3D cell culture model than curcumin. Compounds 2a and 2a-B altered cell cycle progression, increasing the population of cells in the G2/M and S phases, and induced apoptosis in a time- and concentration-dependent manner. Comparative analysis with previously reported data identifies compound 2a as a promising candidate for further investigation due to its high selectivity for malignant versus normal bladder epithelial cells.

Abstract:Curcumin is a versatile natural compound that has been extensively studied for its potential activity in cancer models. However, its clinical development faces challenges, including poor water solubility, chemical instability under physiological conditions, rapid metabolism, and limited systemic bioavailability. These issues have driven efforts to modify the curcumin structure to enhance stability, pharmacokinetics, and target interaction, while preserving or improving its antiproliferative effects. This review highlights key medicinal chemistry strategies for creating analogs beyond curcumin, including (i) monocarbonyl variants that replace the β-diketone group to improve stability, (ii) aromatic ring modifications that adjust electronic properties, lipophilicity, and cellular entry, (iii) prodrug designs that conceal phenolic groups to increase solubility or permeability, and (iv) hybrid molecules and conjugates for dual targeting or better delivery. Additionally, we discuss metal-curcumin(oid) complexes as promising options to modify stability, redox activity, and biological effects in cancer models. We also propose a basic evaluation toolkit to support more consistent comparisons among analogs, emphasizing the need to report chemical stability, microsomal metabolism, selectivity, and in vivo exposure, alongside in vitro viability/proliferation readouts and, where available, orthogonal cytotoxicity endpoints. Rather than treating beyond-curcumin chemistry as a catalog of potency-improving modifications, this review frames the major scaffold classes in terms of developability, evidentiary burden, and translational pragmatism. Overall, successful translation will depend less on isolated IC50 gains and more on standardized profiling and alignment of mechanism claims with achievable exposure.

Flavone–thiazole–aryl hybrid molecules based on 6-aminoflavone and 5-arylidene-4-aminothiazol-2(5H)-ones were synthesized and subjected to physicochemical and biological studies. Microwave-assisted synthesis was performed in two steps. First, an aminolysis reaction of isorhodanine with 6-aminoflavone was carried out to achieve the corresponding hybrid flavone-thiazole 3, which was later subjected to a Knoevenagel condensation with selected aromatic aldehydes, yielding 5-arylidene derivatives 5a–5i. The resulting hybrids were purified and characterized by UV–Vis, NMR, and HR-MS (ESI). In the UV–Vis spectra of all compounds, two characteristic bands were noted. The UV–Vis spectra in DMF of the studied flavone–thiazole–aryl hybrids consist of two major bands with maxima appearing at 280–288 nm, corresponding to band II and 383–399 nm, corresponding to band I, which clearly distinguish them from the large group of modified flavonoids. Among the compounds tested on human bladder cancer 5637 cells, (5Z)-5-[(4-hydroxyphenyl)methylene]-4-[(4-oxo-2-phenyl-chromen-6-yl)amino]thiazol-2-one (5b) exhibited interesting micromolar activity (IC50 2.37 µM). In addition, four of the tested compounds (3, 5f, 5d, and 5b) presented noteworthy antiplasmodial activity against P. falciparum in the low micromolar range (IC50 1.90–4.90 µM). The obtained group of flavone–thiazole–aryl hybrid molecules constitutes valuable starting points for further structural optimisation, which could usher in future novel active pharmaceutical ingredients and pave the way for novel therapeutic strategies.

In the present article, a library of novel non-symmetrical di-/tri-methoxy-aryl-substituted mono-spiro-1,2,4,5-tetraoxanes (5a-m) has been prepared from methyltrioxorhenium(VII) complex-catalysed two-step one-pot direct oxidation approach. The in vitro antiplasmodial and cytotoxic potentials of all non-symmetrical di-/tri-methoxy-aryl-substituted mono-spiro-1,2,4,5-tetraoxanes (5a-m) have been assessed against the chloroquine-resistant FcB1 strain of Plasmodium falciparum, HeLa, A549 and A2780 cancer cells. The in vitro biological assessment has afforded eight di-/tri-methoxy-aryl-substituted mono-spiro-1,2,4,5-tetraoxane derivatives (5b-e, 5g, 5i, 5k-l) with nanomolar antiplasmodial activity (IC50 = 34-91 nM and Selectivity Index = 109-2900). Along with this, two tri-OMe-aryl substituted mon-spiro-1,2,4,5-tetraoxane analogues (5i and 5l) have also shown dual potency with strong antiplasmodial (5i, IC50 = 46 nM; 5l, IC50 = 48 nM), and in vitro micromolar cytotoxicity against the A2780 ovarian cancer (5i, IC50 = 3.82 μM; 5l, IC50 = 1.98 μM) and HeLa cells (5i, LD50 = 10.85 μM; 5l, LD50 = 5.8 μM). In addition, potential drug-target interactions prediction for representative compounds (5d, 5i, and 5l) has been examined using different computational-based techniques. Through this study, the selective incorporation of functionalized di-/tri-methoxy-aryl moieties on the mon-spiro-1,2,4,5-tetraoxane skeleton has proved efficient in improving the overall biological activities of the resulting molecules.

Cancer remains one of the most significant health issues worldwide. By designing compounds with anticancer activity characterized by high selectivity towards cancer cells, medicinal chemistry focuses on the protection of healthy cells and tissues. In this study, we present the hybrid pharmacophore approach, which afforded a series of new pyrrole flavones. The synthetic strategy was based on the Paal-Knorr pyrrole synthesis, starting from aminoflavones through their condensation with 1,4-diketones and leading to 6- and 7-(pyrrol-1-yl) flavones. The isolated products underwent characterization using NMR and UV–VIS spectroscopy, mass spectrometry, TGA, DSC, and Microtox analyses. For all pyrrole flavones, single crystals were obtained and subjected to X-ray diffraction experiments. Their cytotoxic activity was assessed on two human bladder cancer cell lines (5637 and HT-1376) and one non-cancerous (MRC-5) cell line, showing the potential as anticancer agents. Flavone derivative with the 6-(2-methyl-5-phenylpyrrol-1-yl) moiety was active in the MTT assay towards 5637 and HT-1376 cancer cells after 24 h of incubation with IC50 values of 2.97 µM and 5.89 µM, respectively. Notably, flavone derivative with 7-(2-methyl-5-phenylpyrrol-1-yl) revealed cytotoxic activity towards 5637 and HT-1376 cells with IC50 values of 7.39 µM and 13.54 µM, respectively, without any effect on the viability of MRC-5 cells.

6-Mercaptopurine (6MP) commonly occurs in the treatment for acute lymphoblastic leukemia in children. The drug faces several limitations related to low bioavailability and short half-life. In order to overcome the drawbacks of conventional therapeutic systems for 6MP, innovative drug delivery systems are sought. The drug contains sulfur atoms capable of forming coordination bonds with metal ions, e.g., zinc. Hence, this study presented a bioactive glass doped with zinc ions as a carrier for 6MP. The research has demonstrated the carrier's ability to sorption and then desorption as a controlled release. The drug is evenly distributed, suggesting that the doses released from it will always be similar. Drug release in a neutral environment is prolonged at controlled doses, while in an acidic environment, it is immediate. The viability of MCF-7 cells was significantly inhibited when treated with bioactive glass doped with zinc and 6MP. The results indicate the high potential of the material for use in targeted anticancer therapy.

Fungal infections pose a significant global health problem, affecting 20–25% of the population and contributing to over 3.75 million deaths annually. Clotrimazole (CLO) is a widely used topical antifungal drug, but its efficacy is limited by poor penetration through the stratum corneum. Microneedle (MN) systems, composed of micron-scale structures arranged on a patch, offer a promising strategy to overcome the outermost skin barrier and enhance drug penetration into deeper layers. However, optimizing MN design, particularly in terms of size, shape, and fabrication technology, is essential for efficient drug delivery. This study aimed to develop CLO-coated MN systems using an Liquid Crystal Display (LCD)-based 3D printing technique and a thin-film dip-coating method. A comprehensive optimization of printing parameters, including anti-aliasing, layer thickness, curing time, and printing angle, was conducted to ensure the desired mechanical properties. The optimized MNs were coated with either suspension or ethanol-based CLO-hydrogels, with ethanol hydrogel demonstrating superior characteristics. Additionally, the study investigated how microneedle geometry and coating formulation influenced drug release. Antifungal activity against reference and clinical origin Candida albicans strains varied significantly depending on the coating formulation. Finally, the acute toxicity test confirmed no significant toxic effects on Aliivibrio fischeri, indicating the potential biocompatibility and safety of the developed MN-based drug delivery system.

By the use of suitable delivery systems and pharmaceutical formulations, improved transportation of photosensitizers to cancer cells in photodynamic therapy can be achieved. The aim of our study was to demonstrate controlled, redox-triggered release of a photosensitizer by developing a redox- and photo-responsive polymeric carrier system based on poly(lactic-co-glycolic acid) functionalized with cystamine and protoporphyrin IX, which could serve as a model for potential use in photodynamic therapy. During the study, polymeric materials based on cystamine-protoporphyrin IX combination incorporated in poly(lactic-co-glycolic acid) were obtained, characterised in physicochemical studies and subjected to biological assessment. The presence of cystamine enabled the PPIX release in the presence of thiol triggers. The physicochemical characterisation of the new material was performed using UV-Vis, IR, NMR spectroscopies, X-Ray diffraction, and thermogravimetric analysis. The size and morphology of the obtained material were determined using nanoparticle tracking analysis, as well as SEM and TEM microscopy. The photochemical properties and stability of the material were analysed by establishing the singlet oxygen generation and photodecomposition quantum yields. The acute toxicity of modified polymeric material was determined using the Microtox® test, whereas cyto- and photocytotoxicities were assessed in vitro on the human prostate cancer cell line (LNCaP) and human lung fibroblast (MRC-5). The polymer components, cystamine and PLGA, did not affect cell viability on their own, neither upon irradiation nor in the absence of light. The obtained polymeric material based on a protoporphyrin IX-cystamine molar ratio of 1:1 in PLGA could be considered a prospective formulation for PDT. The novelty of our study lies in the design of a dual-responsive (redox and light) PLGA-based carrier system encapsulating protoporphyrin IX and a redox-cleavable linker, enabling controlled, photo-triggered release of the photosensitizer.

Introduction. HO-1 is a stress-responsive enzyme involved in cellular protection against oxidative damage, inflammation, and tissue injury. However, in cancer, its cytoprotective functions may paradoxically support cancer progression, immune evasion, and therapy resistance. Material and methods. This review explores current findings on HO-1’s dual role in cancer biology. We analysed studies addressing its function in redox regulation, angiogenesis, immune modulation, iron metabolism, and its impact on treatment response. Particular focus was placed on HO-1’s downstream metabolites (CO, biliverdin/bilirubin, and iron) and their influence on tumour development. Results. HO-1 contributes to cellular defence by limiting reactive oxygen species and supporting DNA repair. However, its overexpression in tumours promotes survival signalling, angiogenesis (via VEGF and HIF-1α), metabolic reprogramming, and resistance to apoptosis and chemotherapy. Additionally, HO-1 regulates ferroptosis by modulating intracellular iron and lipid peroxidation. The Nrf2/HO-1 axis is frequently upregulated in tumours, enhancing antioxidant capacity and undermining therapeutic efficacy. Preclinical studies show that HO-1 inhibition—via gene silencing, small molecules, or combination with chemotherapy and photodynamic therapy—can restore treatment sensitivity and suppress tumour growth. Conclusions. HO-1 plays a context-dependent, dual role in cancer as both a protector and promoter. Therapeutic targeting of HO-1 holds promise but requires precision to avoid disrupting its protective roles in normal tissues. Further research should aim to develop selective, tumour-specific HO-1 inhibitors and integrate them into combination treatment strategies.

Background/Objectives: Novel boron dipyrromethene derivatives with a heterocyclic, benzoxadiazole substituent were obtained as potential candidates for the photodynamic therapy (PDT) of cancers. Photochemical properties (e.g., singlet oxygen generation quantum yields (ΦΔ), absorption, and emission spectra) and cytotoxic activity studies in normoxic and hypoxic conditions were performed to verify the potential of novel BODIPYs as photosensitizers for PDT. Methods: Obtained dyes were characterized using mass spectrometry and various NMR techniques. The relative method with Rose Bengal as a reference and 1,3-diphenylisobenzofuran as a singlet oxygen quencher was used to determine ΦΔ values. The in vitro studies were conducted on human ovarian carcinoma (A2780) and human breast adenocarcinoma (MDA-MB-231) cells. Results: Photochemical studies showed that the presence of benzoxadiazole moiety only slightly affected the localization of the absorption maxima but resulted in fluorescence quenching compared with meso-phenyl-substituted analogs. In addition, brominated and iodinated analogs revealed a high ability to generate singlet oxygen. Anticancer studies showed high light-induced cytotoxicity of BODIPYs containing heavy atoms with very low IC50 values in the 3.5–10.3 nM range. Further experiments revealed that both compounds also demonstrated phototoxic activity under hypoxic conditions. The most potent cytotoxic effect in these conditions was observed in the iodinated BODIPY analog with IC50 values of about 0.3 and 0.4 μM for A2780 and MDA-MB-231 cells, respectively. Conclusions: The results of this study highlighted the advantages and some potential drawbacks of BODIPY compounds with heavy atoms and benzoxadiazole moiety as a useful scaffold in medicinal chemistry for designing new photosensitizers.

Although curcumin is a well-known natural polyphenol with many biological activities, its clinical application has been limited by low aqueous solubility and stability. Therefore, curcumin derivatives have been proposed to overcome these limitations and increase anticancer activity. This study tested curcumin derivatives with modified feruloyl moieties (2a and 2a-B) and the β-diketo moiety (2a-B) to better understand their anticancer mechanism against human bladder cancer cells. The anticancer activity of 2a and 2a-B was determined using MTT (hypoxic conditions) and LDH (normoxic conditions) assays. An ELISA-based protein panel was used to find the potential molecular targets, while flow cytometric, colorimetric, fluorescent, and luminescent assays were used to investigate the cell death mechanism. It was shown that compound 2a exerted a more potent cytotoxic effect under hypoxic conditions, while compound 2a-B demonstrated a comparable effect in normoxic and hypoxic conditions. The potential molecular targets modified by 2a and 2a-B depending on oxygen concentration were also proposed. Both compounds alter cell cycle progression by blocking the cell cycle in the G2/M phase and decreasing the percentage of cells in the G0/G1 phase. Compound 2a-B led to phosphatidylserine translocation, increased caspase 3/7 activity, and decreased mitochondrial membrane potential, suggesting a mitochondrial apoptosis pathway. We found that the Akt signaling pathway may modulate the activity of compound 2a-B, as evidenced by enhanced cytotoxic activity in combination with MK-2206, an Akt 1/2/3 inhibitor. Thus, our results provide new insights into the anticancer activity of compounds 2a and 2a-B; however, further studies are needed to better understand their therapeutic potential.

Photodynamic therapy (PDT) is a selective tumor treatment that consists of a photosensitive compound—a photosensitizer (PS), oxygen, and visible light. Although each component has no cytotoxic properties, their simultaneous use initiates photodynamic reactions (PDRs) and sequentially generates reactive oxygen species (ROS) and/or free radicals as cytotoxic mediators, leading to PDT-induced cell death. Nevertheless, tumor cells develop various cytoprotective mechanisms against PDT, particularly the adaptive mechanism of antioxidant status. This review integrates an in-depth analysis of the cytoprotective mechanism of detoxifying ROS enzymes that interfere with PDT-induced cell death, including superoxide dismutase (SOD), catalase, glutathione redox cycle, and heme oxygenase-1 (HO-1). Furthermore, this review includes the use of antioxidant enzymes inhibitors as a strategy in order to diminish the antioxidant activities of tumor cells and to improve the effectiveness of PDT. Conclusively, PDT is an effective tumor treatment of which its effectiveness can be improved when combined with a specific antioxidant inhibitor.

The lesson from many studies investigating the efficacy of targeted therapy in glioblastoma (GBM) showed that a future perspective should be focused on combining multiple target treatments. Our research aimed to assess the efficacy of drug combinations against glioblastoma stem cells (GSCs). Patient-derived cells U3042, U3009, and U3039 were obtained from the Human Glioblastoma Cell Culture resource. Additionally, the study was conducted on a GBM commercial U251 cell line. Gene expression analysis related to receptor tyrosine kinases (RTKs), stem cell markers and genes associated with significant molecular targets was performed, and selected proteins encoded by these genes were assessed using the immunofluorescence and flow cytometry methods. The cytotoxicity studies were preceded by analyzing the expression of specific proteins that serve as targets for selected drugs. The cytotoxicity study using the MTS assay was conducted to evaluate the effects of selected drugs/candidates in monotherapy and combinations. The most cytotoxic compounds for U3042 cells were Disulfiram combined with Copper gluconate (DSF/Cu), Dacomitinib, and Foretinib with IC50 values of 52.37 nM, 4.38 µM, and 4.54 µM after 24 h incubation, respectively. Interactions were assessed using SynergyFinder Plus software. The analysis enabled the identification of the most effective drug combinations against patient-derived GSCs. Our findings indicate that the most promising drug combinations are Dacomitinib and Foretinib, Dacomitinib and DSF/Cu, and Foretinib and AZD3759. Since most tested combinations have not been previously examined against glioblastoma stem-like cells, these results can shed new light on designing the therapeutic approach to target the GSC population.

Cancers present a significant medical problem despite the development of medical and pharmaceutical sciences leading to a search for further therapeutic approaches. One such approach could involve the use of curcumin or its derivatives. Curcumin reveals interesting antineoplastic effects that could help in the treatment of cancer diseases. However, this natural product possesses some limitations which prevent its application in medicine. Among its limitations, it is characterized by poor water solubility, low stability, and unsatisfactory bioavailability. Aiming to improve the pharmacokinetic properties and enhance the biological effects of curcumin, a series of 30 chemical compounds inspired by its structure was synthesized and characterized. New compounds were subjected to a preliminary MTT viability assessment of 5637 and SCaBER bladder cancer cell lines. Some derivatives revealed the cytotoxic activities already at the concentration of 1 µM. The most active compounds showed no significant acute toxicity in the Microtox test. Intracellular uptake on the basis of the fluorescent properties of the new compounds was analyzed. It was also found that the presence of the morpholine group in the structure improved the biological activity of studied curcumin derivatives. As selected compounds could be considered potential drug candidates, further studies are necessary towards recognition of the exact mechanism of cellular action, the in vivo stability, and toxicity.