Isosteric Replacement of Sulfur to Selenium in a Thiosemicarbazone: Promotion of Zn(II) Complex Dissociation and Transmetalation to Augment Anticancer Efficacy.

We implemented isosteric replacement of sulfur to selenium in a novel thiosemicarbazone (PPTP4c4mT) to create a selenosemicarbazone (PPTP4c4mSe) that demonstrates potentiated anticancer efficacy and selectivity. Their design specifically incorporated cyclohexyl and styryl moieties to sterically inhibit the approach of their Fe(III) complexes to the oxy-myoglobin heme plane. Importantly, in contrast to the Fe(III) complexes of the clinically trialed thiosemicarbazones Triapine, COTI-2, and DpC, the Fe(III) complexes of PPTP4c4mT and PPTP4c4mSe did not induce detrimental oxy-myoglobin oxidation. Furthermore, PPTP4c4mSe demonstrated more potent antiproliferative activity than the homologous thiosemicarbazone, PPTP4c4mT, with their selectivity being superior or similar, respectively, to the clinically trialed thiosemicarbazone, COTI-2. An advantageous property of the selenosemicarbazone Zn(II) complexes relative to their thiosemicarbazone analogues was their greater transmetalation to Cu(II) complexes in lysosomes. This latter effect probably promoted their antiproliferative activity. Both ligands down-regulated multiple key receptors that display inter-receptor cooperation that leads to aggressive and resistant breast cancer.

Multi-modal mechanisms of the metastasis suppressor, NDRG1: Inhibition of WNT/ß-catenin signaling by stabilization of protein kinase Cα.

The metastasis suppressor, N-myc downstream regulated gene-1 (NDRG1), inhibits pro-oncogenic signaling in pancreatic cancer (PC). This investigation dissected a novel mechanism induced by NDRG1 on WNT/ß-catenin signaling in multiple PC cell types. NDRG1 overexpression decreased ß-catenin and downregulated glycogen synthase kinase-3ß (GSK-3ß) protein levels and its activation. However, ß-catenin phosphorylation at Ser33, Ser37, and Thr41 are classically induced by GSK-3ß was significantly increased after NDRG1 overexpression, suggesting a GSK-3ß-independent mechanism. Intriguingly, NDRG1 overexpression upregulated protein kinase Cα (PKCα), with PKCα silencing preventing ß-catenin phosphorylation at Ser33, Ser37, and Thr41, and decreasing ß-catenin expression. Further, NDRG1 and PKCα were demonstrated to associate, with PKCα stabilization occurring after NDRG1 overexpression. PKCα half-life increased from 1.5 ± 0.8 h (3) in control cells to 11.0 ± 2.5 h (3) after NDRG1 overexpression. Thus, NDRG1 overexpression leads to the association of NDRG1 with PKCα and PKCα stabilization, resulting in ß-catenin phosphorylation at Ser33, Ser37, and Thr41. The association between PKCα, NDRG1, and ß-catenin was identified, with the formation of a potential metabolon that promotes the latter ß-catenin phosphorylation. This anti-oncogenic activity of NDRG1 was multi-modal, with the above mechanism accompanied by the downregulation of the nucleo-cytoplasmic shuttling protein, p21-activated kinase 4 (PAK4), which is involved in ß-catenin nuclear translocation, inhibition of AKT phosphorylation (Ser473), and decreased ß-catenin phosphorylation at Ser552 that suppresses its transcriptional activity. These mechanisms of NDRG1 activity are important to dissect to understand the marked anti-cancer efficacy of NDRG1-inducing thiosemicarbazones that upregulate PKCα and inhibit WNT signaling.

Differential transmetallation of complexes of the anti-cancer thiosemicarbazone, Dp4e4mT: effects on anti-proliferative efficacy, redox activity, oxy-myoglobin and oxy-hemoglobin oxidation.

The di-2-pyridylthiosemicarbazone (DpT) analogs demonstrate potent and selective anti-proliferative activity against human tumors. The current investigation reports the synthesis and chemical and biological characterization of the Fe(iii), Co(iii), Ni(ii), Cu(ii), Zn(ii), Ga(iii), and Pd(ii) complexes of the promising second generation DpT analog, di-2-pyridylketone-4-ethyl-4-methyl-3-thiosemicarbazone (Dp4e4mT). These studies demonstrate that the Dp4e4mT Co(iii), Ni(ii), and Pd(ii) complexes display distinct biological activity versus those with Cu(ii), Zn(ii), and Ga(iii) regarding anti-proliferative efficacy against cancer cells and a detrimental off-target effect involving oxidation of oxy-myoglobin (oxy-Mb) and oxy-hemoglobin (oxy-Hb). With regards to anti-proliferative activity, the Zn(ii) and Ga(iii) Dp4e4mT complexes demonstrate facile transmetallation with Cu(ii), resulting in efficacy against tumor cells that is strikingly similar to the Dp4e4mT Cu(ii) complex (IC50: 0.003-0.006 µM and 72 h). Relative to the Zn(ii) and Ga(iii) Dp4e4mT complexes, the Dp4e4mT Ni(ii) complex demonstrates kinetically slow transmetallation with Cu(ii) and intermediate anti-proliferative effects (IC50: 0.018-0.076 µM after 72 h). In contrast, the Co(iii) and Pd(ii) complexes demonstrate poor anti-proliferative activity (IC50: 0.262-1.570 µM after 72 h), probably due to a lack of transmetallation with Cu(ii). The poor efficacy of the Dp4e4mT Co(iii), Ni(ii), and Pd(ii) complexes to transmetallate with Fe(iii) markedly suppresses the oxidation of oxy-Mb and oxy-Hb. In contrast, the 2 : 1 Dp4e4mT: Cu(ii), Zn(ii), and Ga(iii) complexes demonstrate facile reactions with Fe(iii), leading to the redox active Dp4e4mT Fe(iii) complex and oxy-Mb and oxy-Hb oxidation. This study demonstrates the key role of differential transmetallation of Dp4e4mT complexes that has therapeutic ramifications for their use as anti-cancer agents.

Steric Blockade of Oxy-Myoglobin Oxidation by Thiosemicarbazones: Structure-Activity Relationships of the Novel PPP4pT Series.

The di-2-pyridylketone thiosemicarbazones demonstrated marked anticancer efficacy, prompting progression of DpC to clinical trials. However, DpC induced deleterious oxy-myoglobin oxidation, stifling development. To address this, novel substituted phenyl thiosemicarbazone (PPP4pT) analogues and their Fe(III), Cu(II), and Zn(II) complexes were prepared. The PPP4pT analogues demonstrated potent antiproliferative activity (IC50: 0.009-0.066 µM), with the 1:1 Cu:L complexes showing the greatest efficacy. Substitutions leading to decreased redox potential of the PPP4pT:Cu(II) complexes were associated with higher antiproliferative activity, while increasing potential correlated with increased redox activity. Surprisingly, there was no correlation between redox activity and antiproliferative efficacy. The PPP4pT:Fe(III) complexes attenuated oxy-myoglobin oxidation significantly more than the clinically trialed thiosemicarbazones, Triapine, COTI-2, and DpC, or earlier thiosemicarbazone series. Incorporation of phenyl- and styryl-substituents led to steric blockade, preventing approach of the PPP4pT:Fe(III) complexes to the heme plane and its oxidation. The 1:1 Cu(II):PPP4pT complexes were inert to transmetalation and did not induce oxy-myoglobin oxidation.

Quantification of Bioactive Metabolites Derived from Cell-Free Supernatant of Pediococcus acidilactici and Screening their Protective Properties in Frankfurters.

The specific aims of the current study were to determine and quantify the bioactive compounds derived from the cell-free supernatant (CFS) of Pediococcus acidilactici and screen their protective effect in frankfurters by applying an edible coating. This was achieved by immersing the peeled frankfurters in the CFS (CFS: 50% and 100%) alone or in combination with chitosan (CH: 0.5% and 1%) solutions for 3 min. Untreated frankfurter samples (control) exceeded the maximum acceptable total viable count limit (7.0 log10) on the 14th day, whereas samples treated with 100% CFS + 1% chitosan reached the limit on day 28 during refrigerated storage (P < 0.05). This treatment provided a 14-day extension to the shelf life of frankfurters without causing any significant changes in color and sensory attributes (P > 0.05). Additionally, this treatment inhibited oxidation in the frankfurters, leading to no significant changes in TBA and TVB-N within this group during storage (P > 0.05). This protective effect was mainly attributed to the wide variety of bioactive compounds identified in the CFS, including a total of 5 organic acids, 20 free amino acids, 11 free fatty acids, 77 volatiles, and 10 polyphenols. Due to these bioactive compounds, CFS exhibited a strong radical scavenging capacity (DPPH: 435.08 TEAC/L, ABTS: 75.01 ± 0.14 mg TEAC/L; FRAP: 1.30 ± 0.03 mM FE/L) and antimicrobial activity against microorganisms primarily responsible for the spoilage of frankfurters. In conclusion, the results indicate that the CFS contains high levels of bioactive metabolites, and an edible chitosan coating impregnated with CFS can be utilized to extend the shelf life of frankfurters through its antimicrobial effects and oxidation stabilization.

Inhibitory effect of bioactive compounds derived from freeze-dried paraprobiotic of Pediococcus acidilactici against food-borne pathogens: In-vitro and food model studies.

It was aimed to assess the antimicrobial potential of lyophilized/freeze-dried paraprobiotic (LP) of P. acidilactici against some food-borne pathogens under in-vitro conditions and food model, and determination of bioactive compounds that contribute to the antimicrobial activity of LP. For this purpose, minimum inhibitory concentration (MIC), inhibition zones were determined against Listeria monocytogenes, Salmonella Typhimurium and Escherichia coli O157:H7. The MIC value was 6.25 mg/mL and a 20 µL LP displayed 8.78 to 10.0 mm inhibition zones against these pathogens. In the food matrice challenge, two concentrations of LP (3% and 6%) alone or in combination with EDTA (0.02 M) were added to pathogenic bacteria spiked meatballs, and antimicrobial activity of LP was also determined during refrigerated storage. 6% LP + 0.02 M EDTA treatment provided 1.32 to 3.11 log10 CFU/g reductions in the numbers of these pathogens (P < 0.05). Furthermore, this treatment provided significant reductions on psychrotrophs, TVC, LAB, mold-yeast, and Pseudomonas spp. over the storage (P < 0.05). Regarding characterization results, LP contained contained a wide variety of bioactive compounds, including 5 organic acids (2.15 to 30.64 g/100 g), 19 free amino acids (6.97 to 699.15 mg/100 g), free fatty acids (short-, medium-, and long-chain fatty acids), 15 polyphenols (0.03 to 383.78 mg/100 g), and some volatile compounds such as pyrazines, pyranone and pyrrole derivatives. These bioactive compounds are not only involved in antimicrobial activity but also contribute to the free radical scavenging activity according to the DPPH, ABTS and FRAP assays. In conclusion, the result revealed that the LP improved the chemical and microbiological quality of foods due to containing biologically-active metabolites involved in antimicrobial and antioxidant capacity.

Final-year medical student mental wellness during preparation for the examination for specialty in Turkey: a cross-sectional survey study.

BACKGROUND: In Turkey, most final-year medical students prepare for the Examination for Specialty in Medicine in a high-stress environment. To the best of our knowledge, this is the first study on final-year medical student general psychological distress during preparation for the Examination for Specialty in Turkey. We aim to evaluate psychological distress and understand the variables associated with depression, anxiety, and stress levels among final-year medical students preparing for the Examination for Specialty. METHODS: A self-reporting, anonymous, cross-sectional survey with 21 items consisting of demographic variables, custom variables directed for this study, and the DASS-21 was utilized. Survey results were expounded based on univariate analysis and multivariate linear regression analysis. RESULTS: Our study revealed four variables associated with impaired mental wellness among final-year medical students during preparation for the examination for Specialty: attendance to preparatory courses, duration of preparation, consideration of quitting studying, and psychiatric drug usage/ongoing psychotherapy. DISCUSSION: Considering that physician mental wellness is one of the most crucial determinants of healthcare quality, impaired mental wellness among future physicians is an obstacle to a well-functioning healthcare system. Our study targets researchers and authorities, who should focus on medical student mental wellness, and medical students themselves.

Multi-target activity of copper complexes: Antibacterial, DNA binding, and molecular docking with SARS-CoV-2 receptor.

A series of pendant-armed mixed-ligand copper(II) complexes of the type [CuL1-3(diimine)] (1-6) have been synthesized by the reaction of pendant-armed ligands N,N-bis(2-(((E)-2-hydroxy-5-methylbenzylidene)amino)ethyl)benzamide (H2L1), N,N-bis(2-(((E)-2-hydroxy-5-methylbenzylidene)amino)ethyl)-4-nitrobenzamide (H2L2) and N,N-bis(2-(((E)-2-hydroxy-5-methylbenzylidene)amino)ethyl)-3,5-dinitrobenzamide (H2L3) with diimine = 2,2'-bipyridyl (bpy) or 1,10-phenanthroline (phen) in the presence of copper(II) chloride and analyzed using various spectroscopic methods. All the spectroscopic results support that the complexes adopt a pentagonal-bipyramidal shape around the copper ion. Gram-positive and Gram-negative bacteria were used to test all the complexes for antibacterial activity and all the complexes had greater potency against gram-negative pathogens. DNA-binding experiments of complexes with calf thymus DNA revealed a major-groove binding pattern, further supported by molecular docking studies. Complexes have significantly interacted with SARS-CoV-2 receptor via π-π, π-σ, π-alkyl, π-anion, π-cation, alkyl, hydrogen bond, van der Waals, and electrostatic interactions. The estimated binding energy and inhibition constant of these complexes are higher than standard drugs, chloroquine, and molnupiravir.

Designing Tailored Thiosemicarbazones with Bespoke Properties: The Styrene Moiety Imparts Potent Activity, Inhibits Heme Center Oxidation, and Results in a Novel "Stealth Zinc(II) Complex".

A novel, potent, and selective antitumor agent, namely (E)-3-phenyl-1-(2-pyridinyl)-2-propen-1-one 4,4-dimethyl-3-thiosemicarbazone (PPP44mT), and its analogues were synthesized and characterized and displayed strikingly distinctive properties. This activity was mediated by the inclusion of a styrene moiety, which through steric and electrochemical mechanisms prevented deleterious oxy-myoglobin or oxy-hemoglobin oxidation relative to other potent thiosemicarbazones, i.e., di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC) or di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT). Structure-activity relationship analysis demonstrated specific tuning of PPP44mT electrochemistry further inhibited oxy-myoglobin or oxy-hemoglobin oxidation. Both PPP44mT and its Cu(II) complexes showed conspicuous almost immediate cytotoxicity against SK-N-MC tumor cells (within 3 h). In contrast, [Zn(PPP44mT)2] demonstrated a pronounced delay in activity, taking 48 h before marked antiproliferative efficacy was apparent. As such, [Zn(PPP44mT)2] was designated as a "stealth Zn(II) complex" that overcomes the near immediate cytotoxicity of PPP44mT or its copper complexes. Upon examination of the suppression of oncogenic signaling, [Zn(PPP44mT)2] was superior at inhibiting cyclin D1 expression compared to DpC or Dp44mT.

Radiomics-based machine learning models for prediction of medulloblastoma subgroups: a systematic review and meta-analysis of the diagnostic test performance.

BACKGROUND: Medulloblastomas are a major cause of cancer-related mortality in the pediatric population. Four molecular groups have been identified, and these molecular groups drive risk stratification, prognostic modeling, and the development of novel treatment modalities. It has been demonstrated that radiomics-based machine learning (ML) models are effective at predicting the diagnosis, molecular class, and grades of CNS tumors. PURPOSE: To assess radiomics-based ML models' diagnostic performance in predicting medulloblastoma subgroups and the methodological quality of the studies. MATERIAL AND METHODS: A comprehensive literature search was performed on PubMed; the last search was conducted on 1 May 2022. Studies that predicted all four medulloblastoma subgroups in patients with histopathologically confirmed medulloblastoma and reporting area under the curve (AUC) values were included in the study. The quality assessments were conducted according to the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) and Checklist for Artificial Intelligence in Medical Imaging (CLAIM). A meta-analysis of radiomics-based ML studies' diagnostic performance for the preoperative evaluation of medulloblastoma subgrouping was performed. RESULTS: Five studies were included in this meta-analysis. Regarding patient selection, two studies indicated an unclear risk of bias according to the QUADAS-2. The five studies had an average CLAIM score and compliance score of 23.2 and 0.57, respectively. The meta-analysis showed pooled AUCs of 0.88, 0.82, 0.83, and 0.88 for WNT, SHH, group 3, and group 4 for classification, respectively. CONCLUSION: Radiomics-based ML studies have good classification performance in predicting medulloblastoma subgroups, with AUCs >0.80 in every subgroup. To be applied to clinical practice, they need methodological quality improvement and stability.

New oxovanadium(IV) complexes overcame drug resistance and increased in vitro cytotoxicity by an apoptotic pathway in breast cancer cells.

In order to examine the anticancer potential of oxovanadium(IV) complexes with thiosemicarbazone, two new complexes were prepared starting from 2-thenoyltrifluoroacetone-S-methylthiosemicarbazone. The complexes with tetradentate thiosemicarbazone ligand were characterized by elemental analysis, IR, ESI MS, and single-crystal X-ray diffraction analysis. Cytotoxicity on breast cancer cells, MDA-MB-231 and MCF-7, was determined by MTT assay. Cisplatin was positive control and the results were compared with those of the normal cells, HUVEC and 3T3. The complexes exhibited greater activity on cancer cells than cisplatin, but they were cytotoxic at several times higher concentrations in the healthy cells. In our study, the presence of thiophene and fluoro groups in the oxovanadium(IV) complexes with thiosemicarbazone increased greatly the cytotoxic activity of the complexes on breast cancer cells. Moreover, the complexes induced apoptosis-mediated cell death and also reduced the expression of MDR-1 or P-glycoprotein and ABCG2. As a result, the findings indicated that the complexes have selective cytotoxicity on breast cancer cells and can overcome multidrug resistance. These properties of the complexes make it possible to be a potential anticancer drug candidate for breast cancer treatment.

Three-dimensional digital evaluation of tooth symmetry and volume in patients with missing and peg-shaped maxillary lateral incisors.

INTRODUCTION: This study aimed to evaluate the 3-dimensional tooth crown symmetry and the crown volumes of maxillary and mandibular teeth in patients with unilateral or bilateral missing or peg-shaped maxillary lateral incisors. METHODS: Six groups were established for the possible clinical variations in patients with unilateral missing or peg-shaped maxillary lateral incisors, bilateral presence of these tooth anomalies, and a control group (CG) with normal lateral incisors. The study was conducted on digital dental models of 132 patients. The morphologic symmetry of the antimere teeth was investigated using 3-dimensional deviation analysis. Volumes of contralateral teeth were compared within and among groups for the maxilla and mandible. Furthermore, volumes of teeth were compared in missing and peg-shaped quadrants and quadrants of CG. Intergroup differences were tested using one-way analysis of variance and Kruskal-Wallis tests, whereas paired t and Wilcoxon tests were used for parametric and nonparametric variables, respectively, for intragroup comparisons. RESULTS: Significant deviations in symmetry of antimere teeth were not detected (P >0.05). The volumes of mandibular central and lateral incisors in missing or peg-shaped lateral incisor groups were smaller than in the CG (P <0.05). Per quadrant analysis, volumes of the maxillary central incisor and mandibular central incisors, canines, and first molars in quadrants with missing or peg-shaped lateral incisors were smaller than in the control quadrants (P <0.05). CONCLUSIONS: Neither unilateral nor bilateral presence of missing or peg-shaped maxillary lateral incisors affected the morphologic symmetry of antimere teeth but did affect tooth volume, especially in the mandibular arch.

Characterization of lactic acid bacteria postbiotics, evaluation in-vitro antibacterial effect, microbial and chemical quality on chicken drumsticks.

The aims of this study were to characterize postbiotics, and to evaluate their antibacterial effects in-vitro and on chicken drumsticks. Postbiotics [Pediococcus. acidilactici (PA), Latilactobacillus sakei/Staphylococcus xylosus (LS)] exhibited strong antioxidant activity, and their total phenolic contents were found as 2952.78 ± 0.4 and 1819.44 ± 0.39 mg GAE/L, respectively (P < 0.05). A total of 19 different phenolic and flavonoids were determined in the postbiotics. The results of the study revealed that 5% and 10% postbiotics + EDTA decreased the number of L. monocytogenes nearly 5.0 log10 in 6 h in TSB. S. Typhimurium count in the chicken drumstick decontaminated with 10% PA was found as 2.1 log10 lower than the control group on day 0. L. monocytogenes counts in the chicken drumstick decontaminated with 10% Postbiotics+1% LA groups were found to be 1.1 log10 lower than the control group (P < 0.05). The lowest total mesophilic aerobic bacteria counts in the chicken drumsticks were found in the 10% Postbiotics+1% LA samples, and postbiotics did not change the color properties of the drumstick samples on day 0 (P > 0.05). In conclusion, postbiotics and their combinations with natural preservatives may be an alternative approach to reduce the food-borne pathogens and to extend the shelf-life of poultry meat and meat products.

Impact of chitosan embedded with postbiotics from Pediococcus acidilactici against emerging foodborne pathogens in vacuum-packaged frankfurters during refrigerated storage.

The objective of the study was to carry out characterization of postbiotics from Pediococcus acidilactici and to assess their efficacy (50% and 100%) in combination with chitosan (0.5 and 1%) against Escherichia coli O157:H7, Salmonella Typhimurium, Listeria monocytogenes on frankfurters during refrigerated storage for 35 days. High amounts of total phenolic content (1708.15 ± 93.28 mg GAE/L) and carboxylic acids, which comprised 74.89% of the total volatiles, were found in the postbiotics. On day 0, the postbiotic-chitosan combinations decreased the E. coli O157:H7, L. monocytogenes and S. Typhimurium counts ranging from 1.58 to 3.21 log10 compared to the control in frankfurters (P < 0.05). Total viable count and number of lactic acid bacteria were effectively reduced in all treatment groups (P < 0.05), and postbiotic and chitosan treatments did not cause any changes in pH and color of the frankfurters. In conclusion, postbiotic-chitosan combinations can be used to reduce the risks that might be associated with E. coli O157:H7, L. monocytogenes, and S. Typhimurium in frankfurters.

New thiosemicarbazone-based Zinc(II) complexes. In vitro cytotoxicity competing with cisplatin on malignant melanoma A375 cells and its relation to neuraminidase inhibition.

New thiosemicarbazone-based zinc(II) complexes were synthesized to study their cytotoxicity on A375 malignant melanoma cells. The complexes containing salicylidene (Zn1a), 3-methoxy-salicylidene (Zn1b) or 4-methoxy-salicylidene (Zn1c) moiety were characterized by analytical and spectroscopic methods. Anticancer potential of the complexes was determined by MTT test and HUVEC endothelial cells line was used to comprehend the effect on normal cells. Zn1b with an IC50 of 13 µM was found to be highly cytotoxic against A375 cancer cells, more effective than cisplatin (IC50: 37 µM). Zn1a and Zn1c did not have a negative effect on cell viability in the normal cells and gave the impression that they are more advantageous than cisplatin in this respect. Further, the ability of Zn1a-c to inhibit neuraminidase enzyme and its role in cytotoxicity was discussed. The test revealed that the Zn1b with 3-methoxy substituent exhibited higher inhibition activity against the neuraminidase than the Zn1a and Zn1c as analogical to the cytotoxicity results. In neuraminidase inhibition, IC50 values of Zn1b and Zn1c were 14 and 66 µM, respectively. These concentrations were very close to the cytotoxicity concentrations for Zn1b and Zn1c. The findings may indicate the role of neuraminidase enzyme inhibition in cell death for Zn1b and Zn1c.

The iron(III) and nickel(II) complexes with tetradentate thiosemicarbazones. Synthesis, experimental, theoretical characterization, and antiviral effect against SARS-CoV-2.

The discovery of new inhibitors that can be used in the treatment of viral diseases, including Covid-19, is an area open to research, and there is a need for innovative compounds with increased efficiency that provide inhibition by suppressing enzyme, and receptor mechanisms. The iron(III) and nickel(II) complexes were synthesized by template condensation of 4-methoxy-salicylaldehyde with S-methylthiosemicarbazone derivatives of 1,1,1-trifluoroacetylacetone (for Fe1) and methylacetoacetate (for Ni1). The complex structures having N2O2-chelating thiosemicarbazidato ligand were identified by analytical, spectroscopic, and X-ray crystallography results. Coordination environment of iron(III) center in complex Fe1 has a distorted square pyramidal geometry consisting of the N2O2 donor set and a chlorine atom, while that of Ni1 is square plane with the set. Inhibitory effect of Fe1 compound against SARS-CoV-2 virus specific 3C-like protease enzyme was investigated experimentally. It was determined that the highest inhibition concentration of Fe1 was 100 µM. Percent inhibition activity at this concentration was on average 30.62 ± 3.809%. Binding of both compounds to the 3C-like protease enzyme specific to the SARS-CoV-2 virus was analyzed using docking calculations. As a result of the docking calculation of Fe1, it has been observed that the compound has a binding energy of -7.4 kcal / mol to 3CL-like protease. It has been observed that the protein amino acids GLY143, THR26, and ASN142 contribute to the high binding affinity of the Fe1. The experimental and theoretical results obtained for the two complexes support each other.

Characterization of Pediococcus acidilactici postbiotic and impact of postbiotic-fortified chitosan coating on the microbial and chemical quality of chicken breast fillets.

This study was carried out to characterize antioxidant activity, total phenolic content, and the phenolic and flavonoids profile of postbiotic of Pediococcus acidilactici and to evaluate the effects of postbiotics (10% and 50%) alone and in combination with chitosan coating (1%) on the microbial and chemical quality of chicken breast fillets during storage at 4 °C. Antioxidant activity and total phenolic content of the postbiotics were found to be 1291.02 ± 1.5 mg/L TEAC and 2336.11 ± 2.36 mg/L GAE, respectively. The most abundant phenolic was vanillic acid, followed by t-caffeic, gallic, and caftaric acids. The postbiotic-chitosan (50% + 1%) combination decreased L. monocytogenes and S. Typhimurium counts by 1.5 and 2.1 log10 CFU/g, respectively, compared to the control (P < 0.05). This combination decreased the total viable count (TVC), lactic acid bacteria (LAB), and psychrotrophic bacteria count compared to the control (P < 0.05). No differences were found in thiobarbituric acid (TBA) values among the samples during storage (P > 0.05). Postbiotic treatment did not significantly change the pH values and color properties of the breast fillets (P > 0.05). Postbiotic-chitosan combinations extended the shelf-life by up to 12 days compared to the control. In conclusion, the postbiotic-chitosan combination can be used to preserve and improve the microbial quality of chicken meat products.

Iron(III) and nickel(II) complexes of tetradentate thiosemicarbazones: Synthesis, structure, cytotoxicity, and lipophilicity.

Eighteen of the iron(III) and nickel(II) complexes with tetradentate thiosemicarbazidato ligands were synthesized and described, by analytical and spectroscopic methods. Two complexes as an example to the iron and nickel centered ones were crystallographically analyzed to confirm the molecular structures. Cytotoxic effects of the complexes on K562 chronic myeloid leukemia cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. For comparison, human umbilical vein endothelial cells (HUVECs) was used as a noncancerous cell line. While four of the iron(III) complexes exhibited the antileukemic effect with 50% inhibition of cell growth (IC50 ) values in the 3.4 to 6.9 µg/mL range on K562 cell line, the nickel(II) complexes showed no significant effect on both cell lines. The complexes Fe4, Fe5, and Fe6, bearing 4-methoxy substituent exhibited relatively high antiproliferative activity on both cell lines. Complex Fe3 with 3-methoxy and S-allyl groups exhibited a selectivity between K562 and HUVEC cells by IC50 values of 6.9 and >10 µg/mL, respectively. Lipophilicity, a key parameter for bioavailability and oral administration, was found in the range of -0.3 and +1.3 that desired for drug active ingredients. The results were discussed in the context of a structure-activity relationship.

Structural analysis and biological functionalities of iron(III)- and manganese(III)-thiosemicarbazone complexes: in vitro anti-proliferative activity on human cancer cells, DNA binding and cleavage studies.

One iron(III) and two manganese(III) complexes based on thiosemicarbazone were synthesized and characterized using analytical and spectroscopic data. The crystallographic analysis showed the square pyramid structures of the complexes. Electronic spectra analysis was performed to determine the nature of the interaction between the complexes and calf thymus DNA (CT-DNA). DNA cleavage activities of the complexes were examined by gel electrophoresis (pBR322 DNA). The cytotoxicity of the complexes was determined against human cervical carcinoma (HeLa) and human colorectal adenocarcinoma (HT-29) cell lines by MTT assay. The results indicated that complex Fe1 is bound to CT-DNA via the intercalation mode, while complexes Mn1 and Mn2 are bound to CT-DNA via groove binding and/or electrostatic interactions rather than the intercalation mode. In addition, they showed good binding activity, which followed the order of Fe1 > Mn2 > Mn1. Complexes were found to promote the cleavage of DNA from supercoiled form (SC, Form I) to nicked circular form (NC, Form II) without concurrent formation of Form III, revealing the single-strand DNA cleavage. No significant cleavage was found in the presence of Mn1 and Mn2; however, it was observed at 2000 and 3000 µM concentrations of Fe1. The ability of Fe1 to cleave DNA was greater than that of other complexes and these results are in conformity with their DNA-binding affinities. Cytotoxicity determination tests revealed that the complex Fe1 on HeLa and HT-29 cells exhibited a higher anti-proliferative effect than Mn1 and Mn2 (Fe1 > Mn2 > Mn1). These studies suggested that the complex Fe1 could be a good candidate as a chemotherapeutic drug targeting DNA.