Nowadays, the search for new pharmaceuticals has resulted in the development of thousands of new substances. One of the effective drug design strategies is to modify a previously obtained and studied substance. A very popular modification is the introduction of halogens into the structure of drugs, most often of which being fluorine or chlorine atoms. However, the introduction of bromine into the structure of a potential drug also has a number of advantages. A good example would be natural substances extracted from marine organisms, which have been studied and proven to be effective against various diseases, including antibiotic therapy of resistant bacteria. Numerous studies justify the usage of bromine and its isotopes in therapy (both in diagnostic imaging and radiotherapy). To better explain the impact of “bromination,” numerous researchers have described such a phenomenon as “halogen bond.” Due to the presence of the so-called “sigma-hole” in the halogen atom of an organic molecule, it is possible to form these bonds, which results in a change in intermolecular and intramolecular interactions. Such changes can favorably affect drug-target interactions. The advantages of “bromination” include an increase in therapeutic activity, a beneficial effect on the metabolism of the drug, and an increase in its duration of action. Besides, the phenomenon of the heavy atom effect can be used to increase the effectiveness of photodynamic therapy and radiosensitization. Unfortunately, “bromination” is not without it’s drawbacks, which may include increased toxic effects and accumulation in the organism.

Curcumin has been modified in various ways to broaden its application in medicine and address its limitations. In this study, we present a series of curcumin-based derivatives obtained by replacing the hydroxy groups in the feruloyl moiety with polyethylene glycol (PEG) chains and the addition of the BF₂ moiety to the carbonyl groups. Tested compounds were screened for their cytotoxic activity toward two bladder cancer cell lines, 5637 and SCaBER, and a noncancerous cell line derived from lung fibroblasts (MRC-5). Cell viability was analyzed under normoxic and hypoxic conditions (1% oxygen). Structure–activity relationships (SARs) are discussed, and curcumin derivatives equipped within feruloyl moieties with 3-methoxy and 4-{2-[2-(2-methoxyethoxy)ethoxy]ethoxy} substituents (5) were selected for further analysis. Compound 5 did not affect the viability of MRC-5 cells and exerted a stronger cytotoxic effect under hypoxic conditions. However, the flow cytometry studies showed that PEGylation did not improve cellular uptake. Another observation was that the lack of serum proteins limits the intracellular uptake of curcumin derivative 5. The preliminary mechanism of action studies indicated that compound 5 under hypoxic conditions induced G2/M arrest in a dose-dependent manner and increased the expression of stress-related proteins such as p21/CIP1, phosphorylated HSP27, ADAMTS-1, and phosphorylated JNK. In summary, the results of the studies indicated that PEGylated curcumin is a more potent compound against bladder cancer cell lines than the parent compound, and derivative 5 is worthy of further investigation to clarify its mechanism of anticancer action under hypoxic conditions.

This work presents the synthesis and characterization of metal-free, zinc (II), and cobalt (II) porphyrins substituted with short PEG chains. The synthesized compounds were characterized by UV-Vis, ¹H and ¹³C NMR spectroscopy, and MALDI-TOF mass spectrometry. The origin of the absorption bands for tested compounds in the UV-Vis range was determined using a computational model based on the electron density functional theory (DFT) and its time-dependent variant (TD-DFT). The photosensitizing activity was evaluated by measuring the ability to generate singlet oxygen (ΦΔ), which reached values up to 0.54. The photodynamic activity was tested using bladder (5637), prostate (LNCaP), and melanoma (A375) cancer cell lines. In vitro experiments clearly showed the structure–activity relationship regarding types of substituents, their positions in the phenyl ring, and the variety of central metal ions on the porphyrin core. Notably, the metal-free derivative 3 and its zinc derivative 6 exerted strong cytotoxic activity toward 5637 cells, with IC₅₀ values of 8 and 15 nM, respectively. None of the tested compounds induced a cytotoxic effect without irradiation. In conclusion, these results highlight the potential value of the tested compounds for PDT application.

Curcumin has long been used for health purposes and is currently attracting significant research interest. In this study, we present a series of curcumin derivatives featuring structural modifications, including methoxy groups, short alcohol chains, and bromine atoms. The cytotoxic activity of the compounds obtained was tested against BA/F3 wt, BA/F3 del52, BA/F3 ins5, K562, Jurkat, HCT-116, and MDA-MB-231 cell lines and non-cancerous Balb/3T3 fibroblast lines. The most promising compounds 2a, 6a, and 9a demonstrated anticancer activity comparable to that of doxorubicin, while exhibiting toxicity toward fibroblasts similar to natural curcumin. In addition, thanks to microscopic fluorescence analysis, a mechanism of action was proposed for the most active compounds against the HCT-116 cell line. Some compounds exhibit moderate or strong proapoptotic activity, while others are characterized by cytostatic activity. Studied compounds demonstrated the DNA-intercalation ability and increased the content of cellular ROS in treated HCT-116 cells.

Stilbenes are a group of polyphenols that are gaining steady attention and have promising biological activity. While much attention is given to polyhydroxy compounds derived from resveratrol, other substituents remain largely unexplored. In this work, we present the results of studies on the synthesis, physicochemical characterisation, and ADME parameters simulation of polymethoxy and brominated stilbenes. We also examined their anticancer activity and found that some of the brominated compounds reveal desirable properties. While the brominated derivatives are not significantly more active than the polymethoxy derivatives, they were found to be safer for the tested pseudo-normal cell lines.