Monika Kadela-Tomanek

Type 2 diabetes mellitus (T2DM) remains a major clinical challenge, with postprandial hyperglycemia (PPG) playing a key role in the development of vascular complications. Current pharmacotherapies often do not sufficiently control PPG, highlighting the need for complementary strategies. One effective approach is the inhibition of carbohydrate digesting enzymes, α-amylase and α-glucosidase, which delays glucose absorption and reduces PPG excursions. Flavonoids, a diverse class of plant-derived polyphenols, exhibit multiple biological activities relevant to T2DM, including enzyme inhibition, antioxidant, and anti-inflammatory effects. This review summarizes the mechanisms by which flavonoids modulate glucose metabolism, with particular emphasis on their interactions with α-amylase and α-glucosidase. Structure–activity relationships are discussed, focusing on the influence of hydroxylation patterns, conjugation, and molecular planarity on inhibitory potency and selectivity. Selected flavonoids—chrysin, apigenin, luteolin, and quercetin—are comparatively analyzed in terms of enzyme inhibition profiles, binding mechanisms, and selectivity. Evidence from in vitro studies, enzyme kinetics, and molecular docking highlights their differential activity, particularly the preferential inhibition of α-glucosidase over α-amylase, which may reduce gastrointestinal side effects. Overall, flavonoids represent promising modulators of PPG. However, their clinical relevance is limited by bioavailability and variability of experimental data, warranting further investigation.

Flavones are natural substances widely distributed in fruits and vegetable. Their compounds are characterized by a broad spectrum of activities, including antioxidant activity. Their most interesting biological effect, however, is antihyperglycemic activity, mediated by the inhibition of α-glucosidase. A series of 7-hydroxyflavone derivatives was synthesized and comprehensively characterized using nuclear resonance magnetic spectroscopy. The biological potential of the synthesized derivatives was assessed through antioxidant (DPPH) and α-glucosidase inhibitory assays. The physicochemical and pharmacokinetic properties were analyzed using in silico methods. Finally, molecular docking studies were performed to elucidate the binding mode of compounds within the catalytic site of α-glucosidase.

Cancers, including ovarian cancer, are a growing public health problem due to their high incidence and mortality rates. Ovarian cancer is a particularly challenging neoplasm to diagnose in its early stages due to the absence of specific symptoms and the paucity of effective diagnostic methods. The standard treatment regime for this condition includes surgical intervention, the administration of chemotherapy, and radiation therapy. Flavonoids, a prevalent class of phytonutrients, have been demonstrated to possess a plethora of biological properties, including antioxidant, anti-inflammatory, and anticancer properties. Quercetin, a widely recognised flavonol, has garnered significant attention due to its limited bioavailability, which has prompted the exploration of novel, more active derivatives. Research has demonstrated that structural modifications, incorporating the incorporation of groups comprising single, double or triple bonds, can substantially augment anticancer activity by modulating apoptosis, inhibiting angiogenesis and constraining cancer cell migration. In the course of the study, a series of new quercetin derivatives were synthesised, and their effects on ovarian cancer cells and normal cells were evaluated. Two compounds were selected from among those obtained, which showed particularly strong activity against the OVCAR-3 and SW626 cell lines. Furthermore, thermogravimetric analysis (TGA) was employed to ascertain the thermal stability and physicochemical properties of the compounds under investigation.

Head and neck squamous cell carcinoma (HNSCC) is a therapeutically challenging cancer what underscoring the need for new chemical agents that selectively induce programmed cell death. Fisetin, a naturally occurring flavonoid, exhibits promising anticancer activity but displays limited proapoptotic efficacy and selectivity. Here, we examined whether alkoxylated modification of fisetin enhances its ability to induce apoptosis in HNSCC cells. Fisetin derivatives bearing four-carbon substituents were synthesized and evaluated in multiple HNSCC cell lines. Two derivatives, MKT218 and MKT257, markedly reduced HNSCC cell viability at low micromolar concentrations with low toxicity towards normal human fibroblasts. Notably, the observed cytotoxicity was not associated with activation of a canonical DNA damage response, as neither γH2AX accumulation nor p53 activation was detected. Furthermore, PARP1 cleavage and live-cell imaging combined with annexin V/EthD-III staining revealed a significantly higher proportion of apoptotic cells. The effect was stronger following treatment with MKT218 and MKT257 compared with fisetin. Time-lapse microscopy further demonstrated that fisetin derivatives, particularly MKT218, promote mitosis-associated apoptosis, in contrast to the predominantly cytostatic effect of fisetin. Moreover, in silico docking suggested that MKT218 exerts its pro-apoptotic activity through a multi-target interaction profile involving key regulators of cell survival and apoptosis rather than a single dominant target. To sum up, our findings suggest that alkoxylated fisetin derivatives may be constituted as new non-genotoxic inducers of apoptosis in HNSCC cells.

Chrysin belongs to natural flavonoids characterized wide spectrum of biological activity. Its use in treatment is limited by low bioavailability and rapid metabolism. The structure-activity relationship shows that introduction of substituent at C7 position of flavone scaffold increase the activity and bioavailability. In this study, a series of quinoline-chrysin hybrids was obtained. The structure of compounds was determined using spectroscopic methods. The anticancer activity of compounds was tested against neck and head squamous cell carcinoma lines (HNSCC), while the antioxidant activity was determined using DPPH method. The biological effect depends on the type of quinoline moiety. For the most active compounds, IC₅₀ values as low as ~ 13.8 µM for anticancer activity and ~ 24.5 µM for antioxidant activity were observed. For the most active compounds, their effect on the expression levels of TP53, BAX, and BCL2 genes was examined.

The structure of betulin enables the formation of conjugates that offer improved activity, selectivity, or pharmacokinetic parameters. It was assumed that combining betulin with hippuric acid could produce a product with favorable biological properties. The bond connecting the conjugate elements was an ester group introduced using a method ensuring mild reaction conditions (Steglich method). In this way, betulin and its acetyl derivatives were converted into conjugates with hippuric acid, with good yields. The obtained compounds were assessed for their in vitro antiproliferative activity against seven different human cancer cell lines (MTT and SRB assays), preceded by in silico prediction (PASS online). Lipophilicity (logP_TLC), a significant parameter influencing all stages of the ADME process, was experimentally determined using RP-TLC. LogP_TLC values were compared with logP results obtained from available online computational programs. Antiproliferative activity studies demonstrated the significant sensitivity of MV4-11 cells to the tested compounds. The IC₅₀ values ranged from 4.2 to 31.4 µM. The mechanism of anticancer action was investigated for the most active derivatives 4, 5, and 7. For derivative 7, molecular docking revealed the highest affinity for the FLT3 protein binding site.

Anticancer drug design has been reformed by the creation of heterocyclic hybrids. The introduction of a quinoline scaffold affects the activity, toxicity, and bioavailability of new compounds. The aim of this study was to synthesize and evaluate the biological activity of hybrids of 1,4-naphthoquinone with the 8-hydroxyquinoline moiety. The structure of the new compounds was characterized using spectroscopic methods, such as HR-MS, NMR, and IR. The analysis was supplemented by calculated NMR and IR spectra. The physicochemical properties and bioavailability of the compounds were examined using in silico methods. An analysis of reactivity descriptors showed that the compounds are good electron acceptors and exhibit high reactivity. Bioavailability properties confirm that hybrids could be good oral administration drugs. The biological potential of hybrids was examined by designation of the enzymatic conversion rate of the NQO1 protein and in vitro against cancer cell lines with overexpression of the gene encoding the NQO1 protein. The possibility of interaction between the tested ligand and the NQO1 protein was examined by molecular docking methods.

Chrysin, a naturally occurring flavonoid, exhibits a broad spectrum of biological activities, including showing anticancer properties. However, its clinical application is limited by poor bioavailability and low solubility. The introduction of an amine, amide, ester, or alkoxy group to a flavone skeleton influences the biological activity. This review also discusses hybrid compounds, such as the chrysin–porphyrin hybrid, which are characterized by higher biological activity and better bioavailability properties than single molecules. This review concentrates on the anticancer activity of chrysin and its derivatives against the most popular cancers, such as breast, lung, prostate, and gastrointestinal tumors.

After heart disease, cancer is the second-leading cause of death worldwide. The most effective method of cancer treatment is target therapy. One of the potential goals of therapy could be DT-diaphorase, which reduces quinone moiety to hydroquinone, and reactive oxygen species are create as a byproduct. The obtaining of hybrid compounds containing the quinone moiety and other bioactive compounds leads to new derivatives which can activate DT-diaphorase. The aim of this research was the synthesis and characterization of new hybrids of 5,8-quinolinedione with thymidine derivatives. The analysis of the physicochemical properties shows a strong relationship between the structure and properties of the tested compounds. The enzymatic assay shows that hybrids are good substrates of NQO1 protein. The analysis of the structure–activity relationship shows that the localization of nitrogen atoms influences the enzymatic conversion rate. The analysis was supplemented by a molecular docking study. Comparing the results of the enzymatic assay and the molecular docking presents a strong correlation between the enzymatic conversion rate and the scoring value.

Otyłość to przewlekła choroba, stanowiąca globalny problem i poważne wyzwanie dla zdrowia publicznego. W jej przebiegu dochodzi do nadmiernego nagromadzenia się tkanki tłuszczowej w organizmie, co prowadzi nie tylko do wzrostu ryzyka wystąpienia powikłań zdrowotnych, lecz także negatywnie wpływa na jakość życia. Komórki tłuszczowe – adipocyty – są odpowiedzialne za biosyntezę i uwalnianie adipokin, do których należą m.in. leptyna, wisfatyna, chemeryna oraz omentyna-1. Są to aktywne substancje biologiczne, mogące wykazywać właściwości prozapalne lub przeciwzapalne. Zaburzenie równowagi pomiędzy adipokinami prozapalnymi i adipokinami przeciwzapalnymi może prowadzić do rozwoju zaburzeń metabolicznych. Wspomniane właściwości adipokin sprawiają, że możliwe jest ich potencjalne wykorzystanie jako czynników diagnostycznych oraz terapeutycznych w przebiegu otyłości, a także towarzyszących jej zaburzeń, takich jak insulinooporność, cukrzyca typu 2 czy powikłania kardiometaboliczne. Pomimo znacznego postępu w poznaniu roli, jaką odgrywają omówione adipokiny, konieczne są dalsze badania, których wyniki umożliwią precyzyjne omówienie mechanizmów ich działania oraz określą ścisłe zależności ich stężeń w osoczu od stanu choroby.