Acta Pharmaceutica最新文献

The poor prognosis of glioblastoma multiforme, inadequate treatment options, and growing drug resistance urge the need to find new effective agents. Due to the significant anti-cancer potential of harmicens, hybrid compounds which comprise harmine/β-carboline and ferrocene moiety, we investigated their antiglioblastoma potential in vitro and mechanism of action (inhibition of DYRK1A, Hsp90, anti-oxidative activity). The results have shown that triazole-type harmicens, namely 5, with a ferrocene moiety in C-3 position of the β-carboline ring (IC ₅₀ = 3.7 ± 0.1 µmol L-1, SI = 12.6) and ., the C-6 substituted harmicene (IC ₅₀ = 7.4 ± 0.5 µmol L-1, SI = 5.8) exert remarkable activity and selectivity against human malignant glioblastoma cell line (U251) in vitro. On the other hand, amide-type harmicens 10, 12, and 14 exhibited strong, but non-selective activity, in the low micro-molar range. Mechanistic studies revealed that among active compounds, amide-type harmicens 12 and 14 inhibit DYRK1A and Hsp90 CTD, whereas compound 14 showed pronounced antioxidative activity. Therefore, the antiproliferative activity of harmicens might be a combination of complex molecular interactions.

Since honey has a therapeutic role in the treatment of many diseases, we investigated the content of phenolic compounds and the antioxidant activity in acacia (Robinia pseudoacacia L.), chestnut (Castanea sativa Mill.) and lime-tree (Tilia spp.) honey originating from Croatia and Germany. Total phenols, flavonols, and flavanols contents were observed at higher levels in Croatian Castanea honey compared to German Castanea honey. Significant higher values of total flavanols and hydroxycinnamic acids were measured in Croatian Tilia honey compared to German Tilia honey. For Robinia honey, significantly higher values of total phenols and flavonols were observed in almost all Croatian honey samples compared to German honey. Croatian honey samples had higher antioxidant activity compared to German honey samples with most tested methods. The highest total phenols, total flavanols, ABTS, DPPH, and FRAP values were measured in Castanea honey, then in Robinia honey, and the lowest values in Tilia honey samples. With new developed HPLC method, pinobanksin, pinocembrin, and chrysin were identified in the majority of honey samples. Our results imply that both botanical and geographical origin influence the final quality of phenolic compounds and antioxidant activity in honey. A high positive correlation between the results of antioxidant activity and polyphenols was detected.

Converting macrocycle lactams into bicyclic lactams is proposed as an additional way to further increase the metabolic stability of peptide-based drugs. Unfortunately, the synthesis of bicyclic lactams has to start almost from scratch. This study explores the Hofmann-Löffler-Freytag (HLF) reaction mechanism and products as a potential late-stage functionalisation strategy for facile conversion of macrocyclic to bicyclic ring. Laurolactam, a macrocyclic amide, exhibits significant potential for transformation into bioactive bicyclic structures with smaller, β-, γ-, δ-, and ε-lactam rings, further increasing rigidity and hydrolytic stability. With irradiation provided by a 370 nm lamp, light-induced rearrangement reaction was monitored using nuclear magnetic resonance (NMR), while involved radical intermediates were trapped using N-tert-butyl-α-phenylnitrone (PBN) spin-trap and characterised via EPR. While only two radical adduct types were identified in the electron para magnetic resonance (EPR) (C-centered radical and chlorine radical), all eight possible products are observed in the NMR. Quantum chemical calculations provide deeper insights into reaction thermodynamics and kinetics, explaining why the N-centered radical was not observed. This research highlights the feasibility of using the HLF reaction to transform macrocyclic lactams into stable bicyclic drug candidates, paving the way for new therapeutic developments.

Zeolites are a large family of minerals and the most studied is the naturally occurring clinoptilolite. They possess anti-inflammatory, antioxidant, and detoxifying properties which makes them valuable for medicinal use. Element analysis of zeolite's composition is necessary for its precise chemical characterization, and within this work development of a suspension method for the determination of manga nese, iron, and zinc by total reflection X-ray fluorescence spec-trometry (TXRF) was presented. The Box-Behnken design based on the response surface methodology was applied to determine the optimal sample preparation conditions. The significant variables such as sample amount, volume deposition, and dispersant were selected as critical variables. Based on the results obtained, sample suspensions were prepared by weighing 10 mg of the sample and adding 1 mL of 5 % Triton X-100 with 10 mL Ga as internal standard and deposition volume was set at 10 mL. The results obtained with TXRF were comparable with those obtained with the FAAS method, indicating that this technique can be used instead of the conventional methods. Using the best analytical conditions, the limits of detection for trace elements were in the range of 0.2-0.6 mg kg^-1. Trueness and precision of the results, evaluated by CRM sample analysis, were in most cases acceptable with recoveries values in the range of 104.9-111.4 % and relative standard deviations of 2-10 % (. = 6). Zeolites showed no ability to quench free radicals nor the ability to influence dietary antioxidants.

Electron paramagnetic resonance (EPR) spectroscopy has long been established across various scientific disciplines for characterizing organic radicals, organometallic complexes, protein structures and dynamics, polymerization processes, and radical degradation phenomena. Despite its extensive utility in these areas, EPR spectroscopy's application within pharmaceutical science has historically been constrained, primarily due to factors such as high equipment costs, a steep learning curve, complex spectral deconvolution and analysis, and a traditional lack of emphasis on single-electron chemistry in pharmaceutical research. This review aims to provide a thorough examination of EPR spectroscopy's applications in analyzing a wide array of para-magnetic species relevant to pharmaceutical research. We detail how EPR spectroscopy can be employed to assess free radical scavenging properties in pharmaceutical compounds, elucidate drug mechanisms of action, and explore pharmacokinetics. Additionally, we investigate the role of free radicals in drug-induced toxicity and drug-membrane interactions, while also covering the application of EPR spectroscopy in drug delivery research, advanced studies of metallodrugs, and monitoring of oxygen levels in biological systems through EPR oximetry. The recent advancements in the miniaturization of EPR spectro meters have paved the way for their application in on-site and in-line mo nitoring during the manufacturing process and quality control of pharmaceutical substances and final drug formulations due to being the only direct and non-invasive detection technique for radical detection. Through these discussions, we highlight the substantial contributions of EPR spectroscopy to the advancement of pharmaceutical sciences.

Our study aimed to assess the prevalence of fall risk-increasing drugs (FRIDs) in a sample of community-residing older patients in Croatia and its association with negative health outcomes. An observational, cross-sectional study was conducted on older patients (65+) visiting community pharmacies in three regionally different study sites in Croatia. Data were collected using a questionnaire developed for that purpose and included components of comprehensive geriatric assessment. Prevalence of FRIDs was identified using the "Screening Tool of Older Persons Prescriptions in older adults with high fall risk" (STOPPFall). In the sample of 407 participants (median age 73 (IQR 69-70) years; 63.9 % females), 79.1 % used at least one FRID. The most common drug classes were diuretics, benzodiazepines, and opioids (in 51.1 %, 38.1 %, and 17.2 % participants, respectively). More FRIDs were prescribed to the oldest old patients (85+) and participants from poorer regions of Croatia (Slavonia) (p < 0.05). Exposition to FRIDs was identified as the significant risk factor associated with falls (OR = 1.24 (1.04-1.50); p = 0.020) and higher health-care utilization (OR = 1.29 (1.10-1.51); p = 0.001). Our study highlights the need for rationalization of FRID use. To reduce the unnecessary exposure to FRIDs in older adults, health-care professionals must consider high individualization of medication schemes regarding selection, dosing, and combinations of only necessary FRIDs.

Extracts obtained from common butterbur (Petasites hybridus), standardized to petasins, are existing pharmaceutical options for the treatment and/or prevention of allergic rhinitis (leaves) and migraine (rhizomes). In this study, the total phenolic content, flavonoid content, and antioxidant potential of ten samples of Croatian Petasites species (four P. hybridus, four P. albus, one P. kabli kianus, and one P. paradoxus) obtained by ultrasound-assisted extraction of leaves were compared. The total phenolic content (Folin-Ciocalteu assay) of methanolic leaf extracts ranged from 4.43 ± 0.09 to 10.76 ± 0.60 mg gallic acid equivalent g^-1 dry mass (mg GAE g^-1 DM) for P. hybridus and from 6.66 ± 0.43 to 19.92 ± 2.90 mg GAE g^-1 DM for P. albus samples, while those of P. kablikianus and P. paradoxus were equal to 7.56 ± 0.17 mg GAE g^-1 DM and 10.22 ± 0.46 mg GAE g^-1 DM, respectively. Flavonoid content (AlCl₃ assay) varied between 2.51 ± 0.10 and 4.03 ± 0.08 mg quercetin equivalent g^-1 dry mass (mg QE g^-1 DM) for P. hybridus and between 2.21 ± 0.09 and 5.22 ± 0.02 mg QE g^-1 DM for P. albus samples, while those of P. kablikianus and P. paradoxus were equal to 5.59 ± 0.05 mg QE g^-1 DM and 5.50 ± 0.09 mg QE g^-1 DM, respectively. Antioxidant potential was in high correlation with total phenolic content (r = 0.93, p < 0.001). Due to the expected contribution of plant polyphenols and flavonoids to the activity of butterbur extracts and their observed great variabilities, determining the content of these compounds may be of interest to the pharmaceutical industry.

Biowaste produced in urban parks is composed of large masses of organic matter that is only occasionally used economically. In this work, extracts of six plants widely distributed in urban parks in Central Europe (Achillea millefolium, Cichorium intybus, Malva sylvestris, Medicago sativa, Plantago lanceolata, and Trifolium pratense), prepared using 10 % and 50 % ethanol, were screened for their antidiabetic and related properties. HPLC and UV-Vis analysis revealed the presence of caffeic acid, quercetin, luteolin, and apigenin derivatives. The extracts were active in DPPH antiradical, .-carotene-linoleic acid, ORAC, and reducing power assay. They inhibited lipoxygenase, collagenase, as well as heat-induced ovalbumin coagulation. They were also able to hinder carbohydrate degradation. For example, IC ₅₀ of anti-α-amylase activity of 10 % and 50 % ethanol extract of M. sativa extracts (204.10 ± 2.11 µg mL-1 and 78.27 ± 0.99 µg mL-1, respectively) did not statistically differ from the activity of the positive control, acarbose (284.74 ± 3.81 µg mL^-1). Similar results were observed for their anti-.-glucosidase activity. In most assays, the use of 50 % ethanol was shown to be better suited for the extraction of active metabolites. The results indicate that the biowaste obtained from urban parks represents a potential source of plant material for the preparation of high-value antidiabetic products.

The aim of this study was to determine whether there are differences in complete blood count parameters (CBC) and inflammation-related biomarkers, MPV/PC, PLR, NLR, LWR, LMR, NMR, and LCR, among patients with colorectal carcinoma (CRC) and patients with colorectal adenomas. The study included 155 patients who were divided into two groups according to histopathological analysis - 74 adenomas patients and 81 CRC patients. A routine examination of CBC was conducted on Sysmex XN1000 whereas CRP was measured on Alinity ci-series. Statistical analysis was performed by ROC curve analysis using MedCalc Statistical Software. In CRC patients, hemoglobin concentration, hematocrit, MCV, MCH, and MCHC were lower, while RDW was higher (p < 0.001), compared to patients with adenomas. Total leukocyte count (p = 0 .006), absolute neutrophils (p = 0.005), and absolute monocytes (p = 0.007) were lower while relative eosinophils (p = 0.001) and relative basophils (p = 0.001) were higher in CRC patients. Platelet count (p < 0.001) was significantly higher and MPV (p = 0.003) was significantly lower in CRC patients. Furthermore, MPV/PC (p < 0.001) was significantly lower and PLR (p < 0.001) was significantly higher in CRC. Moreover, Receiver Operating Characteristic (ROC) analysis revealed poor diagnostic accuracy, for all tested parameters (AUC was 0.7 or less). PC, MPV, MPV/PC, and PLR were significantly different between study groups, but ROC analysis revealed poor diagnostic accuracy. Lower hemo globin levels in CRC patients are possibly due to more frequent and excessive bleeding. Higher levels of basophils and eosinophils in CRC patients are indicators of inflammatory reaction, which is linked to CRC.