NAD(P)H:quinone oxidoreductase 1 inducer activity of some novel anilinoquinazoline derivatives

The Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response elements pathway enables cells to survive oxidative stress conditions through regulating the expression of cytoprotective enzymes such as NAD(P)H:quinone oxidoreductase 1 (NQO1). This work presents the design and synthesis of novel anilinoquinazoline derivatives (2–16a) and evaluation of their NQO1 inducer activity in murine cells. Molecular docking of the new compounds was performed to assess their ability to inhibit Keap1–Nrf2 protein–protein interaction through occupying the Keap1–Nrf2-binding domain, which leads to Nrf2 accumulation and enhanced gene expression of NQO1. Docking results showed that all compounds can potentially interact with Keap1; however, 1,5-dimethyl-2-phenyl-4-(2-phenylquinazolin-4-ylamino)-1,2-dihydropyrazol-3-one (9), the most potent inducer, showed the largest number of interactions with key amino acids in the binding pocket (Arg483, Tyr525, and Phe478) compared to the native ligand or any other compound in this series

Cytotoxic effects of Smp24 and Smp43 scorpion venom antimicrobial peptides on tumour and non-tumour cell lines

Smp24 and Smp43 are novel cationic AMPs identified from the venom of the Egyptian scorpion Scorpio maurus palmatus, having potent activity against both Gram-positive and Gram-negative bacteria as well as fungi. Here we describe cytotoxicity of these peptides towards three non-tumour cell lines (CD34+ (hematopoietic stem progenitor from cord blood), HRECs (human renal epithelial cells) and HACAT (human skin keratinocytes) and two acute leukaemia cell lines (myeloid (KG1a) and lymphoid (CCRF-CEM) leukaemia cell lines) using a combination of biochemical and imaging techniques. Smp24 and Smp43 (4–256 µg/mL) decreased the cell viability (as measured by intracellular ATP) of all cells tested, although keratinocytes were markedly less sensitive. Cell membrane leakage as evidenced by the release of lactate dehydrogenase was evident throughout and was confirmed by scanning electron microscope studies

Synthesis and biological evaluation of novel 2-phenylquinazoline-4-amine derivatives:identification of 6-phenyl-8H-benzo[g]quinazolino[4,3-b]quinazolin-8-one as a highly potent inducer of NAD(P)H quinone oxidoreductase 1

A novel series of quinazoline compounds (2-14) incorporating biologically active heterocyclic moieties were designed and synthesized. The structure of the newly synthesized compounds was recognized on the basis of elemental analyses, IR, (1)H-NMR, (13)C-NMR and mass spectral data. All compounds were evaluated for their ability to induce the cytoprotective enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) using a quantitative bioassay and a docking study was performed in the Kelch domain of Keap1 obtained from the Protein Data Bank (PDB ID: 4IQK) to explore the ability of the synthesized compounds to block the Nrf2-binding site of Keap1. All of the synthesized compounds showed concentration-dependent inducer activity with potencies in the low- or sub-micromolar range. Compound 12 was the most potent inducer in this new series, with a concentration that doubles the specific activity of NQO1 (CD value) of 70 nM. The identification of this compound offers a new chemical scaffold for future development of highly potent inducers.</p

NAD(P)H:Quinone oxidoreductase 1 inducer activity of novel 4-aminoquinazoline derivatives

Fourteen novel 4-aminoquinazoline derivatives 2-15 were designed and synthesized. The structure of the newly synthesized compounds was established on the basis of elemental analyses, IR, (1)H-NMR, (13)C-NMR, and mass spectral data. The compounds were evaluated for their potential cytoprotective activity in murine Hepa1c1c7 cells. All of the synthesized compounds showed concentration-dependent ability to induce the cytoprotective enzyme NAD(P)H: quinone oxidoreductase (NQO1) with potencies in the low- to sub-micromolar range. This approach offers an encouraging framework which may lead to the discovery of potent cytoprotective agents.</p

Differences in instructional quality during the Covid-19 pandemic between Oman and Germany and the role of teacher competences

Introduction: School closures during the Covid-19 pandemic hit educational systems worldwide, forcing teachers to switch to digital learning settings. The presented study aims to (a) adapt and evaluate scales on instructional quality in digital settings, (b) describe instructional quality during the pandemic, and (c) to identify predictive teacher competences. Method: Data was assessed in a cross-sectional design via an online questionnaire conducted in Oman and Germany simultaneously. Results: Analyses of data from N = 284 teachers in Oman and Germany revealed mostly good psychometric parameters, differences in instructional quality between both countries, and positive relations between teachers’ competences and instructional quality. Conclusion: The present study contributes to instrument development and to the growing body of research, investigating teaching quality during the pandemic

Antioxidant, hypoglycemic and anti-diabetic activities of Ziziphus spina-christi (L) Willd (Rhamnacae) leaf extract

Purpose: To investigate the antioxidant, hypoglycemic and antidiabetic activities as well as the phenolic composition of Ziziphus spina-christi (ZSC)Methods: Eighty percent methanol extract (ZSC-1), as well as ethyl acetate (ZSC-2), n-butanol (ZSC-3) and aqueous (ZSC-4) fractions were administered orally to mice at doses of 250 and 500 mg/kg of body weight. The hypoglycemic and anti-diabetic activities of these fractions in the treated mice were evaluated after 7 and 15 days, using glibenclamide as a standard. Antioxidant activities in vitro were determined using stable free radical DPPH and ABTS radical scavenging techniques.Results: The strongest (p &lt; 0.001) anti-diabetic activity (25.59 and 39.48 % after 7 and 15 days, respectively) was found following treatment with 500 mg/kg ZSC-3 fraction. Similarly, the highest (p &gt; 0.001) hypoglycemic effect was achieved with 500 mg/kg ZSC-3 treatment (29.07 and 35.56 % after 7 and 15 days, respectively). ZSC-1 possessed the highest content of total flavonoids (36.2 mg/g) and total polyphenol (82.3 mg/g).Conclusion: Fraction ZSC-3 displayed potential hypoglycemic activity while ZSC-1, ZSC-2 and ZSC-3 possess remarkable DPPH scavenging ability equivalent to 89, 96 and 80.3 % of the activity of the standard drug respectively.Keywords: Ziziphus spina, Rhamnaceae, Hypoglycemic, Anti-diabetic, Flavonoids, Polypheno

Pollutant Removal from Highway Runoff Using Retention/Detention Units

Highway runoff contains total suspended solids, hydrocarbons, oil and greases, chloride, and other contaminants that are transported in solution and particulate forms to adjacent floodplains, roadside swales, and retention/detention ponds. Oil and grit chambers represent a type of retention/detention unit used for removing heavy particulates and adsorbed hydrocarbon particulates. Storage/sediment units also represent a type of retention/detention unit used for controlling peak flow and removing suspended solids. The aim of this study is to evaluate the effect of traffic volume and site characteristics on highway runoff quality. The study also aims to evaluate the performance of retention/detention units that collect runoff from the Prague-Brno and Prague-Plzeň highways, Czech Republic. The results of this study indicate no definitive relationship between average daily traffic and concentration of runoff constituents, though the site characteristics have a strong relation to some constituents. The results also show that retention/detention units are effective in treating organic compounds

CLOVE OR GREEN TEA ADMINISTRATION ANTAGONIZES KHAT HEPATOTOXICITY IN RATS

Objective: Khat consumption has become a common problem that affects the health aspects of life in Yemen and other parts in the world. The liver has been suspected to be particularly vulnerable to the harmful effects of khat use and until now khat hepatotoxicity effects are still controversial. This study was conducted to investigate the hepatoprotective effects of aqueous extracts of clove and green tea, as medicinal herbs with established antioxidant properties, against controversial hepatotoxicity effects of khat in rats. Methods: Rats received a daily oral dose of khat extract alone or in combination with green tea or clove extract for six weeks. To study the effects on liver cells, histopathology, routine liver function tests, malondialdehyde (MDA), total antioxidant capacity (TAC) and the activities of superoxide dismutase (SOD) and catalase (CAT) enzymes were investigated. Results: Khat administration showed marked liver injury; congestion in the portal vein with fibrous tissue proliferation, extended from the portal area and forming intralobular Porto-portal bridging fibrous septae. Besides significant routine liver function tests alterations, lipid peroxides elevation, and TAC reduction with significant inhibition of SOD and CAT activities. Conclusion: Combined administration of khat with clove or green tea protected hepatocytes via oxidative stress inhibition. They significantly counteracted the alterations in liver function tests, decreased lipid peroxidation and restored the antioxidant status to near normal levels. These results confirm khat hepatotoxicity and suggest that clove or green tea administration has strong hepatoprotective effects against khat induced hepatotoxicity in rats via antioxidant mediated mechanism.Â