This aimed to develop a comprehensive theoretical protocol for examining substitution reaction processes. The researchers used a theoretical quantum-mechanical protocol based on the QM-ORSA approach, ...which estimates the kinetic parameters of thermodynamically favourable reaction pathways. This theoretical protocol was validated by experimentally investigating substitution mechanisms in two previously synthesised Pd(II) complexes:
-(3-(1-(2-hydroxypropylamino)ethylidene)chroman-2,4-dione)palladium(II) (C1) and
-(3-(1-(2-mercaptoethylamino)-ethylidene)-chroman-2,4dione)palladium(II) (C2), along with biologically relevant nucleophiles, namely L-cysteine (l-Cys), L-methionine (l-Met), and guanosine-5'-monophosphate (5'-GMP). Reactions were investigated under pseudo-first-order conditions, monitoring nucleophile concentration and temperature changes using stopped-flow UV-vis spectrophotometry. All reactions were conducted under physiological conditions (pH = 7.2) at 37 °C. The reactivity of the studied nucleophiles follows the order: l-Cys > l-Met > 5'-GMP, and the reaction mechanism is associative based on the activation parameters. The experimental and theoretical data showed that C2 is more reactive than C1, confirming that the complexes' structural and electronic properties greatly affect their reactivity with selected nucleophiles. The study's findings have confirmed that the primary interaction occurs with the acid-base species L-Cys, mostly through the involvement of the partially negative sulfur atom (87.2%). On the other hand, C2 has a higher propensity for reacting with L-Cys
, primarily through the partially negative oxygen atom (92.6%). The implementation of this theoretical framework will significantly restrict the utilization of chemical substances, hence facilitating cost reduction and environmental protection.
The substitution reactions of Pd (caffeine)2Cl2 and Pt (caffeine)2Cl2 (caffeine = 1,3,7‐trimethylxanthine) complexes with bio‐molecules such as 9‐methylguanine (9‐MetGua) and ...guanosine‐5′‐monophosphate (5′‐GMP) were studied spectrophotometrically. Kinetic measurements were performed under the pseudo‐first‐order conditions at 37°C and pH = 7.2 (25‐mM Hepes buffer) with the addition of 50‐mM NaCl. All reactions were carried out in two reaction steps giving the M (caffeine)2(Nu)2 (M = Pd (II) or Pt (II) and Nu = 5′‐GMP or 9‐MetGua) as the reaction product. The reaction mechanism was also confirmed by nuclear magnetic resonance (NMR) spectroscopy and density functional theory (DFT) calculations. Kinetically data revealed a much higher reactivity of Pd (caffeine)2Cl2 complex compared with analog platinum‐complex, while 9‐MetGua reacted faster than 5′‐GMP. The interactions of Pd (caffeine)2Cl2 and Pt (caffeine)2Cl2 complexes with calf thymus‐DNA (CT‐DNA) and human serum albumin (HSA) were investigated as well. Competitive studies with DNA were performed in the presence of ethidium bromide (EB) and Hoechst dye 33258 (Hoe). The complexes interact with DNA via minor groove rather than by intercalation. High values of binding constants indicate a good binding affinity of complexes toward HSA (104 M−1). Additionally, the experimental results of binding studies between Pt (caffeine)2Cl2 complex with DNA and HSA were compared by a molecular docking study. The cytotoxicity of Pd (caffeine)2Cl2 and Pt (caffeine)2Cl2 complexes was tested against the mouse breast cancer (4T1) and colon cancer (CT26) as well as the human breast cancer (MDA‐MB‐468) and colon cancer (HCT‐116) cell lines. The results indicate that the Pt (caffeine)2Cl2 complex has higher cytotoxic capacity compared with Pd (caffeine)2Cl2 at concentrations higher than 2 μM.
The interactions of Pd (caffeine)2Cl2 and Pt (caffeine)2Cl2 (caffeine = 1,3,7‐trimethylxanthine) complexes with 9‐methylguanine (9‐MetGua), guanosine‐5′‐monophosphate (5′‐GMP), calf thymus‐DNA (CT‐DNA), and human serum albumin (HSA) were studied. Much higher reactivity of Pd (caffeine)2Cl2 complex was noted, while 9‐MetGua reacted faster than 5′‐GMP. The complexes have good binding affinity to DNA and HSA. Both complexes exhibit cytotoxicity against the mouse breast cancer (4T1) and colon cancer (CT26) as well as the human breast cancer (MDA‐MB‐468) and colon cancer (HCT‐116) cell lines.
Toxoplasmosis is a globally distributed parasitic zoonosis, affecting approximately one third of the human population. Epidemiological studies on toxoplasmosis conducted in Serbia so far have been ...focused on women of childbearing age, without a clear insight into the prevalence in the general population. We conducted a cross-sectional study in a representative sample of the healthy adult population consisting of 1095 blood donors of both genders to establish the prevalence and risk factors for Toxoplasma gondii infection. Data on the demographic and clinical characteristics of all study participants, as well as on their lifestyle habits, were collected by means of a questionnaire. The overall prevalence of infection was 20.5% (224/1095) and the avidity of the specific IgG antibodies detected was high in a vast majority of the seropositive donors (98.2%). Interestingly, the remaining 1.8% of the specific IgG positive samples were of borderline avidity (4/224), in complete absence of specific IgM. The multivariate logistic regression analysis showed that independent risk factors included age (from OR (95% CI) 1.9 (1.13−3.28) in the 30−39 age group, to 6.8 (3.27−14.24) in the age group of >60 years), suburban living (OR (95% CI) 2.2 (1.43−3.34)) and contact with soil (OR (95% CI) 1.4 (1.01−1.94)). This first large-scale study on toxoplasmosis in the general population in Serbia shows the lowest prevalence ever reported in this country. Moreover, the novel perspective on risk factors provides an updated basis for future prevention programs.
This study aimed at analyzing and comparing the elemental composition of different parts of cultivated Physalis alkekengi (ljoskavac): rhizome with roots, stem with leaves, fruit, and inflated calyx. ...The contents of twenty- -one macro- and micro-elements were determined by inductively coupled plasma optical emission spectrometry (ICP-OES). In addition, the patterns of the distributions of both macro- and micro-elements were subjected to AHC analysis which gave different grouping of samples in sub-clusters. Generally, potassium, calcium, iron, and aluminum were the most abundant elements, but with different distribution in examined parts. High contents of iron and aluminum were detected in a stem with leaves, followed with samples of rhizome with roots and calyx, while potassium dominates in samples of calyx and stem with leaves. Edible fruits did not contain potentially toxic metals in concentration higher than permissible limits, wherein the lowest contents of lead and aluminum were detected; cadmium was under limit of quantification. Arsenic, mercury, and thallium were below the method detection limit.
Hepatocellular carcinoma (HCC) is one of the most frequent cancers in humans, characterised by a high resistance to conventional chemotherapy, late diagnosis, and a high mortality rate. It is ...necessary to elucidate the molecular mechanisms involved in hepatocarcinogenesis to improve diagnosis and treatment outcomes. The Runt-related (RUNX) family of transcription factors (RUNX1, RUNX2, and RUNX3) participates in cardinal biological processes and plays paramount roles in the pathogenesis of numerous human malignancies. Their role is often controversial as they can act as oncogenes or tumour suppressors and depends on cellular context. Evidence shows that deregulated RUNX genes may be involved in hepatocarcinogenesis from the earliest to the latest stages. In this review, we summarise the topical evidence on the roles of RUNX gene family members in HCC. We discuss their possible application as non-invasive molecular markers for early diagnosis, prognosis, and development of novel treatment strategies in HCC patients.
The ethanol extracts of selected Acinos Miller species were investigated in terms of chemical composition, antimicrobial and antioxidative activities. Qualitative and quantitative analyses of the ...extracts were performed using GC and GC-MS. Eighty-six constituents, accounting for 93.70-99.99% of the total composition of the extracts, were identified. The ethanol extracts of A. majoranifolius, A. suaveolens and A. alpinus were characterized by domination of monoterpenes, representing 85.03%, 57.39% and 28.02% of the total extracts, respectively. Fatty acids and their esters in the A. arvensis and A. graveolens extracts reached 28.97% and 30.75%. Also, n-alkanes were the major compounds found in A. hungaricus ethanol extract (30.98%). The extracts were characterized by determination of total polyphenols, flavonoids and tannins. Besides, the antioxidant activity of the investigated extracts was estimated by two assays: DPPH and FRAP test. The highest antioxidant activity was observed in the extract of A. alpinus which had high levels of all examined polyphenol classes. A disk diffusion method was employed for the determination of the antimicrobial activities of the ethanol extracts. Gram-positive: Bacillus subtilis, Sarcina lutea, Staphylococcus aureus, Clostridium pyogenes, Enterococcus sp., Micrococcus flavus; Gram-negative: Klebsiella pneumoniae, Pseudomonas aerugionsa, Salmonella enteritidis, Proteus vulgaris, Escherichia coli and fungal organisms: Aspergillus niger, Candida albicans and Saccharomyces cerevisiae were used as test microorganisms. The results of preliminary bioassay demonstrated that the A. alpinus ethanol extract could be a possible source of compounds with antioxidant and antimicrobial activity.
•Three novel Ph3Sn(IV) azo-carboxylato compounds were synthesized and characterized.•((E)−4-((4-(dimethylamino)phenyl)diazenyl)benzoato)Ph3Sn(IV), 3, has highest activity.•3 kills all investigated ...tumor cells at lower nanomolar concentrations.•3 induced apoptosis in MCF-7 cells, inhibits cell division and boosts cellular nO.•Compounds interact with calf thymus DNA and bovine serum albumin.
Three novel triphenyltin(IV) compounds with modulated azo-carboxylato ligands: triphenylstannyl (E)-4-((2-hydroxynaphthalen-1-yl)diazenyl)benzoate, 1, triphenylstannyl (E)-4-((4-hydroxyphenyl)diazenyl)benzoate, 2, and triphenylstannyl (E)-4-((4-(dimethylamino)phenyl)diazenyl)benzoate, 3, were synthesized and characterized by elemental analysis, FTIR and NMR (1H, 13C, 119Sn) spectroscopy. The structures and spectra of compounds were predicted by Density Functional Theory (DFT) methods at B3LYP-D3BJ/6–311++G(d,p)(H,C,N,O)/LanL2DZ(Sn) level of theory. Furthermore, the antitumor potential of ligand precursors, HL1–HL3, and appropriate organotin(IV) compounds 1–3 was evaluated across mouse melanoma B16F1, human breast adenocarcinoma MCF-7, human colorectal HT-29 and human prostate PC3 cell lines using MTT and CV assays. The organotin(IV) compounds exhibit enhanced cellular uptake and efficacy in reducing viable cell numbers when compared to free acids. Specifically, compound 3 demonstrates a notable impact at lower nanomolar concentrations on all tested cell lines. Moreover, 3 induces cell death in MCF-7 cells by inhibiting cell division and promoting the overproduction of cellular nitric oxide (NO), ultimately leading to caspase-independent apoptosis. Importantly, this process occurs without concurrent activation of autophagy or the generation of ROS/RNS species. The binding affinity of 1–3 with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) was investigated by fluorescence spectroscopy and molecular docking simulations, suggesting their capacity to interact with these biomolecules.
Three novel triphenyltin(IV) compounds with azo-carboxylato ligands were synthesized and characterized. Notably 3, triphenylstannyl (E)-4-((4-(dimethylamino)phenyl)diazenyl)benzoate, showed significant antitumor potential across various cell lines, inducing caspase-independent apoptosis in MCF-7 cells. Compound 3 exhibited enhanced cellular uptake and interaction potential with biomolecules DNA and BSA, emphasizing its biomedical application potential. Display omitted
Pinus mugo Turra sensu stricto (dwarf mountain pine) is a species native to central and southern Europe, which performs a key role in subalpine areas by preventing avalanches and soil erosion. In ...this study, headspace extraction coupled with GC-MS/FID analyses was used to analyze diversity of needle volatiles in 10 natural populations of P. mugo s. str. growing in the Julian Alps, southern Carpathians and Balkan Peninsula. The multivariate statistical analyses revealed clear differentiation between Julian Alpine and southern Carpathian populations, supporting the hypothesis about existence of vicariant gene pools in these two European mountain chains. Although several earlier studies have pointed out heterogeneity of the Balkan populations, none of the investigated Balkan populations have shown the volatile pattern similar to the Carpathian group, as they all formed a common group with the Alpine population. AHC of bioclimatic data as well as regression analysis suggested that general volatile differentiation in P. mugo s. str. essentially does not represent an adaptive response to bioclimatic, orographic or geological conditions. Therefore, the described population groups might be provisionally considered as two P. mugo s. str. chemotypes. Our findings regarding volatile characters complement those obtained from morpho-anatomical, phytochemical and molecular data reported so far.
Fast determination of the volatile components of widely used culinary herbs and spices, without prior preparation of the sample, using headspace sampling (HS) and GC?MS/FID analysis, is presented. ...Generally, monoterpenes were the dominant class in HS volatiles (HSV): monoterpene hydrocarbons in dill, celery, parsnip and parsley, and oxygenated monoterpenes in coriander, bay laurel and rosemary. The HSV of ginger and clove samples differed from the others due to their high content of sesquiterpene hydrocarbons and phenylpropanoids, respectively. The most extreme case of limited distribution was related to the samples of garlic-HSV comprised organosulfur compounds and none of the above mentioned classes. Furthermore, the HSV data were processed via principal component analysis, making visible the variability and tendency between the investigated samples. Lastly, the research provides insights in many HS profiles of culinary herbs and spices, giving relative representation of volatiles as well as differences and deviation in terms of HSV content.
Toxoplasmosis, caused by the cosmopolitan protozoan Toxoplasma gondii, has particular implications during pregnancy due to the possible transmission of infection to the fetus. Very few studies have ...assessed seroprevalence and the risk factors for toxoplasmosis in healthy pregnant women. The aim of this study was to examine the seroprevalence of T. gondii infection in healthy pregnant women and to identify the associated risk factors for toxoplasmosis. The cross-sectional study involved 300 healthy pregnant women who came to the Institute for Blood Transfusion in Belgrade between November 2018 and February 2019 for routine blood group and Rh factor testing before delivery, who were also tested using serological screening for the presence of specific antibodies. Positives were further examined using enzyme immunoassay. Of the total sera of participants analyzed, 38 were positive for specific IgG, resulting in a seroprevalence rate of 12.7% (95% Confidence Interval (CI) 9.1–17.0%). All pregnant women presented negative anti-T. gondii IgM antibodies. The multivariate logistic regression analysis revealed that living in a house with a garden was independently associated with the risk of T. gondii infections, while eating chicken meat was connected with a lower risk compared to eating other types of meat with an odds ratio (OR) of 2.5 (95% CI 1.21–5.02) and an OR of 0.3 (95% CI 0.09–0.83), respectively. Although the prevalence of anti-T. gondii IgG antibodies is relatively low, it is essential to maintain and adapt evidence-based preventive measures for toxoplasmosis continually.
PDF
