Dizajniranje i sinteza novih derivata tiofenkarbohidrazida, tienopirazola i tienopirimidina s antioksidativnim i antitumorskim djelovanjem

2-Amino-5-acetyl-4-methyl-thiophene-3-carboxylic acid ethyl ester (1) and 5-acetyl-2-amino-4-methylthiophene-3-carbohydrazide (2) were synthesized and used as starting materials for the synthesis of new series of 1-(5-amino-4-(3,5-dimethyl-1H-pyrazole-1-carbonyl)-3-methylthiophen-2-yl) ethanone (3a), 1-(5-amino-4-(4-chloro-3,5-dimethyl-1H-pyrazole-1-carbonyl)-3-methylthiophen-2-yl) ethanone (3b), 1-(4-methyl-2-amino-5-acetylthiophene-3-carbonyl) pyrazolidine-3,5-dione (4), (Z)-N\u27-(4-methyl-2-amino-5-acetylthiophene-3-carbonyl) formohydrazonic acid (5a), (Z)-ethyl-N\u27-(4-methyl-2-amino-5-acetylthiophene-3-carbonylformo hydrazonate (5b), 6-acetyl-3-amino-2,5-dimethylthieno2,3-dpyrimidin-4(3H)-one (8), 5-methyl-3-amino-2-mercapto-6-acetylthieno2,3-dpyrimidin-4(3H)-one (10) and 5-methyl-6-acetyl-2-thioxo-2,3-dihydrothieno2,3-dpyrimidin-4(1H)-one (12) as potential antioxidant and antitumor agents. Pharmacological results showed that compounds 6a, 6b, 8, 10 and 12 exhibited promising antitumor and antioxidant activity.Etilni ester 2-amino-5-acetil-4-metil-tiofen-3-karboksilne kiseline (1) i 5-acetil-2-amino-4-metiltiofen-3-karbohidrazid (2) sintetizirani su i upotrebljeni kao reaktanti u sintezi novih spojeva 1-(5-amino-4-(3,5-dimetil-1H-pirazol-1-karbonil)-3-metiltiofen-2-il) etanona (3a), 1-(5-amino-4-(4-klor-3,5-dimetil-1H-pirazol-1-karbonil)-3-metiltiofen-2-il) etanona (3b), 1-(4-metil-2-amino-5-acetiltiofen-3-karbonil) pirazolidin-3,5-diona (4), (Z)-N\u27-(4-metil-2-amino-5-acetiltiofen-3-karbonil) formohidrazonske kiseline (5a), (Z)-etil-N\u27-(4-metil-2-amino-5-acetiltiofen-3-karbonilformo hidrazonata (5b), 6-acetil-3-amino-2,5-dimetiltieno2,3-dpirimidin-4(3H)-one (8), 5-metil-3-amino-2-merkapto-6-acetiltieno2,3-dpirimidin-4(3H)-ona (10) i 5-metil-6-acetil-2-tiokso-2,3-dihidrotieno2,3-dpirimidin-4(1H)-ona (12) kao potencijalnih antioksidansa i citostatika. Farmakološka ispitivanja ukazuju na to da spojevi 6a, 6b, 8, 10 i 12 imaju značajno antitumorsko i antioksidativno djelovanje

GIZA 11 AND GIZA 12; TWO NEW FLAX DUAL PURPOSE TYPE VARIETIES

Sixteen flax genotypes {13 promising lines and 3 check varieties viz., Giza 8 (oil type), Sakha 1 (dual purpose type) and Sakha 3 (fiber type)} were evaluated for straw, seed, oil yields and their related traits under twelve different environments; four locations (Sakha, Etay El-Baroud, Ismailia and Giza Exp. Stations through three successive seasons (2011/12, 2012/13 and 2013/14). These materials were evaluated in a randomized complete blocks design with three replications at the twelve above-mentioned environments. The analysis of variance revealed highly significant differences among genotypes (G), environments (E) and G x E interaction for all studied traits except straw weight per plant, indicating a wide range of variation among genotypes, environments and these genotypes exhibited differential response to environmental conditions. The significant variance due to residual for all characters except both straw weight per plant and oil yield per fad indicated that genotypes differed with respect to their stability suggesting that prediction would be difficult, which means that mean performance alone would not be appropriate. Interaction component of variance (σ2ge) was less than the genotypic variance (σ2g) for all characters, indicating that genotypes differ in their genetic potential for these traits. This was reflected in high heritability and low discrepancy between phenotypic (PCV) and genotypic (GCV) coefficients of variability values for these traits indicating the possibility of using each of long fiber percentage, plant height and technical stem length as selection indices for improving straw weight per plant, as well as, using 1000-seed weight and capsules number per plant as selection indices for improving seed weight per plant. Yield stability (YSi) statistic indicated that S.541-C/3 and S.541-D/10 gave high mean performance and stability for straw, fiber, seed and oil yields per fad in addition to oil percentage, capsules number per plant and 1000-seed weight. Therefore, the two genotypes well be released under the name Giza 11 and Giza 12, respectively. These newly released varieties are of dual purpose type for straw, fiber, seed and oil yield. They may replace the low yielding cultivars Giza 8, Sakha 1 and Sakha 3

Evaluation of 3-(3-chloro-phenyl)-5-(4-pyridyl)-4,5-dihydroisoxazole as a Novel Anti-Inflammatory Drug Candidate

BACKGROUND: 3-(3-chloro-phenyl)-5-(4-pyridyl)-4,5-dihydroisoxazole (DIC) is a five-membered heterocyclic compound containing a N-O bond. The anti-inflammatory effects of this compound were studied both in vitro and in vivo. PRINCIPAL FINDINGS: DIC effectively decreased TNF-α and IL-6 release from LPS-stimulated macrophages in a dose dependent manner. DIC diminished the levels of COX-2 with subsequent inhibition of PGE(2) production. DIC also compromised HMGB1 translocation from the nucleus to the cytoplasm. Moreover, DIC prevented the nuclear translocation of NF-κB and inhibited the MAPK pathway. In vivo, DIC inhibited migration of neutrophils to the peritoneal cavity of mice. CONCLUSIONS: This study presents the potential utilization of a synthetic compound, as a lead for the development of novel anti-inflammatory drugs

Corporate boards and performance pricing in private debt contracts

This paper investigates the effects of corporate governance on the use of performance pricing in debt contracts on a sample of newly syndicated loans in the U.S. private debt market. While cross-sectional results provide no evidence for the predicted relation between corporate governance quality and the likelihood of using performance pricing in debt contracts, there is evidence for the predicted positive relation between corporate governance quality and the use of interest-increasing performance pricing provisions. Evidence also provides support for the predicted negative relation between corporate governance quality and the use of financial ratio as the measure of performance underlying the provisions. Overall, empirical evidence supports the hypothesis that debt-holders perceive aspects of corporate governance to be beneficial and factor them in their contracting decisions

The Role of Information and Financial Reporting in Corporate Governance and Debt Contracting

We review recent literature on the role of financial reporting transparency in reducing governance-related agency conflicts among managers, directors, and shareholders, as well as in reducing agency conflicts between shareholders and creditors, and offer researchers some suggested avenues for future research. Key themes include the endogenous nature of debt contracts and governance mechanisms with respect to information asymmetry between contracting parties, the heterogeneous nature of the informational demands of contracting parties, and the heterogeneous nature of the resulting governance and debt contracts. We also emphasize the role of a commitment to financial reporting transparency in facilitating informal multiperiod contracts among managers, directors, shareholders, and creditors

The identification of some flax introductions

Volume: 33Start Page: 467End Page: 47

Role of glutathione S-transferase P-1 (GSTP-1) gene polymorphism in COPD patients

Background: COPD is a multifactorial disease. It is a widely distributed disease with high morbidity and mortality, associated with different pathologies. The link between glutathione S-transferase P-1 (GSTP1) polymorphism and COPD needs to be clarified. Objectives: To show the relationship between GSTP1 gene polymorphism and pathogenesis of COPD, and to clarify the role of smoking in GSTP1 gene polymorphism. Patients and methods: This study carried out on 30 COPD patients met the clinical criteria of COPD set by GOLD 2013 and 20 healthy controls. Blood was sampled for studying GSTP1 gene polymorphism by PCR-RFLP. Results: There was a significant difference between group A (COPD smokers) and group B (COPD non smokers) regarding the presence of non mutant and heterozygous mutation. GSTP1 mutation was significantly higher in group C (smoking controls) than group D (non smoking controls). There was a highly significant difference between smoking subjects than non smoking compared with mutation. There was no significant difference in mutation between smokers and ex-smokers. There was no significant difference between studied subjects having heterozygous mutation and subjects without as regards their spirometry results. Conclusion: There is a significant association between GSTP1 gene polymorphism and the development of COPD, and smoking have a role in GSTP1 gene polymorphism. The polymorphism has no relation to disease severity

Elevated tissue transglutaminase antibodies in juvenile idiopathic arthritis children: Relation to neutrophil-to-lymphocyte ratio and disease activity

Background: Subclinical gut inflammation is described in juvenile idiopathic arthritis (JIA), so has joint involvement been related to celiac disease (CD). The well-known involvement of tissue transglutaminase (tTG) in the pathogenesis of CD stimulated progress in the field of autoimmune diseases. Aim of the work: To screen JIA children for tTG antibodies and to detect its relation to the neutrophil-lymphocyte ratio (NLR) and disease activity. Patients and methods: The study included 44 JIA children with 44 matched controls. All subjects had no GIT symptoms suggestive of CD. Disease activity was assessed using the juvenile arthritis disease activity score in 27 joints (JADAS-27). The tTG antibodies (IgA and IgG) were assessed. Results: The patients mean age was 12.5 ± 2.8 years and disease duration 5.01 ± 2.9 years; Female:Male 3.4:1. The mean JADAS-27 score was 12.6 ± 2.04. tTG antibodies were positive in 43.2% of the patients compared to 18.2% control (p = 0.01). Antibodies positivity was comparable according to gender and subtypes. The NLR in JIA children (1.62 ± 0.58) was significantly higher than in control (1.3 ± 0.5) (p = 0.006). Those with positive tTG antibodies had a significantly reduced body mass index (p = 0.02) and increased NLR (p = 0.02) compared to those with negative tTG. Only NLR and JADAS-27 would significantly predict antibodies positivity (p = 0.037 and p = 0.04, respectively). Conclusion: Increased tTG antibodies are frequent in JIA children raising the possibility of an associated subclinical CD. Markedly reduced BMI and increased NLR could forecast the presence of these antibodies. In addition to the JADAS-27, the NLR is a simple test that could predict this association and could be a useful biomarker

Assessment of vascular endothelial growth factor in systemic lupus erythematosus patients with anti-phospholipid syndrome

Aim of the work: The aim of the present study was to assess the serum vascular endothelial growth factor (VEGF) in systemic lupus erythematosus (SLE) patients with and without antiphospholipid syndrome (APS). Relation of the VEGF to the clinical characteristics and laboratory investigations were well thought out. Patients and methods: The study included 84 female SLE patients; 37 with APS and 47 without as well as 33 matched control. Disease activity was estimated using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and damage index evaluated. Serum VEGF level was quantified using ELISA. Results: The mean age of the SLE patients was 29.03 ± 5.4 years with disease duration of 5.2 ± 3.1 years. The VEGF was signficantly higher in the SLE patients (417.1 ± 410.4 pg/ml) compared to the control (76.5 ± 33.01 pg/ml) (p < 0.0001) and was comparable between those with and without APS. VEGF was signficantly higher in those with a positive anti-ds DNA (n = 53) (471.8 ± 431.7 pg/ml) compared to those with a negative test (223.9 ± 234.8 pg/ml) (p = 0.005). The serum VEGF level signficantly correlatied with the SLEDAI (r = 0.34, p = 0.001) and steroid dose (r = 0.27, p = 0.02). On regression analysis, VEGF was not a signficant predictor of disease activity (p = 0.46). A cut off value of 126 pg/ml showed a good sensitivity (72%) and specificity (60%) predicting anti-dsDNA positivity (p = 0.02). Conclusion: Serum VEGF was remarkably increased in SLE patients with no special relation to APS and may be considered a potential marker of disease activity. Further insights on its relation with anti-ds DNA and genotypic expression in SLE are warranted. Keywords: Vascular endothelial growth factor, Systemic lupus erythematosus, Anti-phospholipid syndrome, SLEDAI, SLICC DI, Anti-ds DN

Synthesis, biological evaluation and molecular modeling study of new (1,2,4-triazole or 1,3,4-thiadiazole)-methylthio-derivatives of quinazolin-4(3H)-one as DHFR inhibitors

A new series of 2-mercapto-quinazolin-4-one analogues was designed, synthesized and evaluated for their in vitro DHFR inhibition, antitumor and antimicrobial activity. Compound 17 proved to be the most active DHFR inhibitor with IC value of 0.01 lM, eight fold more active than methotrexate (MTX). Compounds 16 and 24 showed antitumor activity against human Caco2 colon and MCF-7 breast tumor cell lines with IC 50 50 values of 25.4 and 9.5 lg/ml, respectively. Compounds 15, 20, 21 and 30 showed considerable activity against the Gram-positive bacteria Staphylococcus aureus while 24 and 30 proved active against Bacillus subtilis with a magnitude of potency comparable to the broad spectrum antibiotic Ciprofloxacin. Strong activity was observed for 13, 14, 19, 20 and 24 against Candida albicans and Aspergillus flavus. Compound 17 shared a similar molecular docking mode with MTX and made a critical hydrogen bond and arene-arene interactions via Ala9 and Phe34 amino acid residues, respectively