Wajdy Al-Awaida

Structure-activity relationship of novel series of 1,5-disubstituted tetrazoles as cyclooxygenase-2 inhibitors: Design, synthesis, bioassay screening and molecular docking studies.

A novel class of modified 1,5-disubstituted tetrazoles was designed and synthesized, their biological activity as cyclooxygenases inhibitors was screened, and their molecular docking studies were performed. The structural modifications of the first category included the 4-methylsulfonyl phenyl at C-1 of the central moiety and the linkers (-OH, -CH2OH, -CH2CH2OH) with different lengths at the para position of the N-1 phenyl group. For the second category, the 4-methylsulfonyl phenyl group at C-1 was replaced with 4-aminosulfonyl phenyl. While for the third category, a methylene unit was inserted between the C-1 of the tetrazole central ring and the 4-(methylsulfonyl)phenyl group, keeping the same linkers of various extensions at the para position of the N-1 phenyl group. Among the screened compounds, tetrazole 4i showed the best inhibition potency and selectivity values for both COX-2 enzyme (IC50=3μM, SI>67) and COX-1 isoenzyme (IC50>200μM). Compounds 4e, 4h, and 4i, which have the highest inhibition potency toward COX-2 were selected for the molecular docking studies to verify their inhibition and selectivity for COX-2 over COX-1 with their modified structure. The obtained theoretical studies are in agreement with the in vitro bioassay screening results, which supports the importance of the structural modifications for our studied compounds.

Increased Salivary Nitric Oxide and G6PD Activity in Refugees with Anxiety and Stress.

Anxiety and stress are related to physiological changes in humans. Accumulating evidence suggests a cross-talk between psychiatric disorders and oxidative stress. The objective of this study was to compare oxidative stress and defensive antioxidant biomarkers in a group of refugees with acute anxiety and stress with a group of local Jordanians. The Hamilton Anxiety Rating Scale (HAM-A) and the Perceived Stress Scale (PSS) Arabic version were used to assess anxiety and stress respectively. Salivary nitric oxide concentration, glucose-6-phosphate dehydrogenase (G6PD) activity and total salivary protein were compared. As expected, refugees showed higher anxiety and stress scores compared with Jordanians. Also, we report a significant increase in salivary nitric oxide and G6PD activity in the refugee group while total protein concentration did not vary between the two groups. This is the first study that demonstrates an increase in nitric oxide and G6PD activity in the saliva of refugees, thus highlighting their potential role as possible biomarkers in anxiety and stress disorders. Copyright

Molecular Docking Studies and X-ray Structure Determination of 1-{4-(Methylsulfonyl)phenyl}-5-phenyl-1H-tetrazole

The structure of 1-{4-(methylsulfonyl)phenyl}-5-phenyl-1H-tetrazole was determined by Xray crystallography. The latter crystallizes in the monoclinic space group Ia. The cell dimensions of the azole are a = 12.2393 (6) A, b = 12.4076 (6) A, c = 10.0409 (5) A,  = 112.5240 (5)°, V = 1408.50 (12) A 3 , and Z = 4, and its structure was refined to R1 = 0.0230, wR2 = 0.0614. The tetrazole ring is essentially planar, while the aryl rings at the 1- and 5-positions of this compound show consistent twist from the tetrazole plane, with tetrazole-aryl dihedral angles in the range of 38.63(4)° to 47.23(5)°. No strong intermolecular hydrogen bonds were observed. Docking study of the studied tetrazole with cyclooxygenase-2 enzyme was preformed. Amino acid residues in the binding site that interact with the molecule were identified and their interactions with the ligand were discussed.

Salivary Nitric Oxide, a Biomarker for Stress and Anxiety?

Objective To investigate if salivary nitrate correlates to the daily psychological stress and anxiety in a group of human subjects. Methods The convenient sample recruitment method was employed; data from seventy three subjects were analyzed. The Perceived Stress Scale (PSS) and Hamilton Anxiety Rating Scale (HAM-A) inventories were used to determine stress and anxiety scores respectively. Salivary nitric oxide was measured through nitrate (NOx) levels using the Griess reaction method. Results Although stress and anxiety were correlated. No significant correlation exists between salivary nitrate and daily psychological stress and anxiety in the studys participants. Conclusion While all previous studies focused NOx levels in acute stress models. This is the first study to investigate the correlation between salivary nitrates and daily psychological stress and anxiety. Although stress and anxiety were correlated, there is no correlation between salivary nitrates and daily psychological stress and anxiety. Further studies are required to investigate this correlation using other biological samples such as plasma.

Differentially expressed TDFs by cDNA-AFLP in tomato infected with Fusarium oxysporum f. sp. lycopersici

To elucidate the tomato defense responses during the interaction of tomato and Fusarium oxysporum f. sp. lycopersici (Fol), a cDNA-AFLP experiment of the fungal-induced changes at the transcriptional level was performed to identify up- or down-regulated genes. Transcript derived fragments (TDF) from leaves, stems and roots were used for accurate gene expression profiles by visual observation and analysis of bands and their intensities in Fol infected and non-infected tomato lines (AVTO 9802 and AVTO 1002). Using 10 AFLP primer combinations, an average of 163 scored TDFs was identified as differentially expressed genes, corresponding to about 55.7% of all visualized transcripts. These TDFs were consistent with the extensive physiological changes that affect infected tissues from leaves, stems and roots. Although most of the visualized transcripts were affected by infection, about 46.6% of the identified differentially expressed TDFs were down-regulated during infection, possibly reflecting the management of cellular resources and/or the repression of defense responses. Understanding the defense mechanism of plant against pathogens would significantly assist in the development of new resistant tomato cultivars.

In vitro anticancer, anti-inflammatory, and antioxidant potentials of Ephedra aphylla

Purpose: The goal of our study is to test whether a naturally occurring plant, Ephedra aphylla, will show antiproliferative ability against tested cell lines and to test its anti-inflammatory and antioxidative potentials. Materials and Methods: In our study, we used four solvents with different polarities – aqueous, chloroform, methanol, and n-hexane – to extract different compounds from the aerial parts of E. aphylla. Antioxidant activity of E. aphylla was determined by measuring nitric oxide (NO) and hydrogen peroxide (H2O2) scavenging activities. The anti-inflammatory activity was studied using the inhibition of albumin denaturation assay. Finally, the antiproliferative activity of breast cancer cell lines (T47D, MCF-7) and Vero cell line (African green monkey kidney) was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Results: Phytochemical screening for various extracts of E. aphylla showed the presence of medicinally important compounds including cardiac glycosides, alkaloids, triterpenes, tannins, and flavonoids. The scavenging activity for H2O2 of various solvent extracts was in the order of methanol > aqueous > chloroform > ethyl acetate > n-hexane. In addition, E. aphylla solvent extracts also exhibited a scavenging activity for NO in the order of methanol > ethyl acetate > aqueous > chloroform > n-hexane. All of the solvent extracts showed IC50 inhibition of albumin denaturation at a concentration between 209.5 ± 8.1 and 225 ± 11 μg/ml. Moreover, all extracts displayed strong antiproliferative potential against MFC7, T47D tested cell lines and very weak cytotoxic activity against Vero normal cell line. Conclusions: E. aphylla has a promising potential to be used as a drug source for breast cancer treatment based on its strong antiproliferative activity.