Design and synthesis of (2-oxo-1,2-dihydroquinolin-4-yl)-1,2,3-triazole derivatives via click reaction: Potential apoptotic antiproliferative agents

A mild and versatile method based on Cu-catalyzed [2+3] cycloaddition (Huisgen-Meldal-Sharpless reaction) was developed to tether 3,3’-((4-(prop-2-yn-1-yloxy)phenyl)methylene)bis(4-hydroxyquinolin-2(1H)-ones) with 4-azido-2-quinolones in good yields. This methodology allowed attaching three quinolone molecules via a triazole linker with the proposed mechanism. The products are interesting precursors for their anti-proliferative activity. Compound 8g was the most active one, achieving IC$_{50}$ = 1.2 ± 0.2 µM and 1.4 ± 0.2 µM against MCF-7 and Panc-1 cell lines, respectively. Moreover, cell cycle analysis of cells MCF-7 treated with 8g showed cell cycle arrest at the G2/M phase (supported by Caspase-3,8,9, Cytochrome C, BAX, and Bcl-2 studies). Additionally, significant pro-apoptotic activity is indicated by annexin V-FITC staining

Energy harvesting from Microbial Fuel Cells – Wastewater to Electricity

MFCs have the potential to revolutionise wastewater treatment and catalyse a change in attitude towards wastewater as a commodity. It has been observed that domestic wastewater contains approximately 7.6 kJ/L of energy (Heidrich et al., 2011). In large-scale settings, wastewater could be used as an energy resource, offering huge savings in terms of cost and environmental burden. The major challenges facing the implementation of MFCs into wastewater treatment are scale up and energy harvesting/storage. In this study, a modular 20L air-breathing microbial fuel cell was developed alongside a smart energy harvesting (EH) system incorporating AI. The 20L air breathing MFC consists of modular cathode cassettes that enables easy maintenance and scale up to suit adaptive or changing end user requirements. PVDF/Stainless steel mesh cathodes are fabricated using phase inversion and oxygen reduction reaction catalysts incorporated in the polymeric matrix. Custom made carbon fibre brush electrodes are utilised as anodes. The system was inoculated with Shewanella Oneidensis MR-1 and ran under recirculating batch conditions. The MFC is monitored and controlled by a purpose-built circuit that tracks the performance of the individual cathode cassettes and configures the system via a custom Maximum Power Point Tracking (MPPT) algorithm for the best efficiency available for the given conditions. In addition, the circuit stores the extracted energy in a suitable energy storage element such as a capacitor bank or a rechargeable battery pack, with optimum charging levels. Moreover, the system is capable of learning multiple parameters associated with the MFC to optimise its parameters to maintain its high efficiency. The harvested energy can be used to power various types of electronic devices through the circuit's variable/adjustable power output. Heidrich, E., Curtis, T. and Dolfing, J. (2011). Determination of the Internal Chemical Energy of Wastewater. Environmental Science & Technology, 45 (2), 827-832. Available from 10.1021/es103058w

Synthesis of novel amidines via one-pot three component reactions: Selective topoisomerase I inhibitors with antiproliferative properties

Novel series of amidines were synthesized via the interaction between alicyclic amines, cyclic ketones, and a highly electrophilic 4-azidoquinolin-2(1H)-ones without any catalyst or additive. All the obtained products were elucidated based on NMR spectroscopy, mass spectrometry, and elemental analysis. The reaction conditions were optimized using cyclohexanone (2), piperidine (3a), and 4-azido-quinolin-2(1H)-one (1a) under an air atmosphere. The new compounds 4a-l and 5a-c were tested for antiproliferative activity against four cancer cell lines using doxorubicin as a reference drug. The most potent derivatives were compounds 4b, 4d, 4e, 4i, and 5c, with GI$_{50}$ ranging from 1.00 µM to 1.50 µM. Compound 5c was the most effective derivative against the four cancer cell lines, outperforming doxorubicin. The compounds 4b, 4d, 4e, 4i, and 5c were studied further as topoisomerase I and IIα inhibitors. The compounds tested showed selective inhibition of topo I over topo IIα. Finally, docking studies explain why these compounds prefer topo I over topo IIα

Geological and geophysical investigation of Kamil crater, Egypt

We detail the Kamil crater (Egypt) structure and refine the impact scenario, based on the geological and geophysical data collected during our first expedition in February 2010. Kamil Crater is a model for terrestrial small-scale hypervelocity impact craters. It is an exceptionally well-preserved, simple crater with a diameter of 45 m, depth of 10 m, and rayed pattern of bright ejecta. It occurs in a simple geological context: flat, rocky desert surface, and target rocks comprising subhorizontally layered sandstones. The high depth-to-diameter ratio of the transient crater, its concave, yet asymmetric, bottom, and the fact that Kamil Crater is not part of a crater field confirm that it formed by the impact of a single iron mass (or a tight cluster of fragments) that fragmented upon hypervelocity impact with the ground. The circular crater shape and asymmetries in ejecta and shrapnel distributions coherently indicate a direction of incidence from the NW and an impact angle of approximately 30 to 45 . Newly identified asymmetries, including the off-center bottom of the transient crater floor downrange, maximum overturning of target rocks along the impact direction, and lower crater rim elevation downrange, may be diagnostic of oblique impacts in well-preserved craters. Geomagnetic data reveal no buried individual impactor masses >100 kg and suggest that the total mass of the buried shrapnel >100 g is approximately 1050–1700 kg. Based on this mass value plus that of shrapnel >10 g identified earlier on the surface during systematic search, the new estimate of the minimum projectile mass is approximately 5 t.Published1842–18683.8. Geofisica per l'ambienteJCR Journalrestricte

Novel 1,5-diaryl pyrazole-3-carboxamides as selective COX-2/sEH inhibitors with analgesic, anti-inflammatory, and lower cardiotoxicity effects

Funding Information: The authors extend their appreciation to the Deanship of Scientific Research at Jouf University for funding this work through research grant number (DSR2020-04-421 )Peer reviewedPostprin

Design, Synthesis and Biological Evaluation of Syn and Anti-like Double Warhead Quinolinones Bearing Dihydroxy Naphthalene Moiety as Epidermal Growth Factor Receptor Inhibitors with Potential Apoptotic Antiproliferative Action

Our investigation includes the synthesis of new naphthalene-bis-triazole-bis-quinolin-2(1H)-ones 4a–e and 7a–e via Cu-catalyzed [3 + 2] cycloadditions of 4-azidoquinolin-2(1H)-ones 3a–e with 1,5-/or 1,8-bis(prop-2-yn-1-yloxy)naphthalene (2) or (6). All structures of the obtained products have been confirmed with different spectroscopic analyses. Additionally, a mild and versatile method based on copper-catalyzed [3 + 2] cycloaddition (Meldal–Sharpless reaction) was developed to tether quinolinones to O-atoms of 1,5- or 1,8-dinaphthols. The triazolo linkers could be considered as anti and syn products, which are interesting precursors for functionalized epidermal growth factor receptor (EGFR) inhibitors with potential apoptotic antiproliferative action. The antiproliferative activities of the 4a–e and 7a–e were evaluated. Compounds 4a–e and 7a–e demonstrated strong antiproliferative activity against the four tested cancer cell lines, with mean GI50 ranging from 34 nM to 134 nM compared to the reference erlotinib, which had a GI50 of 33 nM. The most potent derivatives as antiproliferative agents, compounds 4a, 4b, and 7d, were investigated for their efficacy as EGFR inhibitors, with IC50 values ranging from 64 nM to 97 nM. Compounds 4a, 4b, and 7d demonstrated potent apoptotic effects via their effects on caspases 3, 8, 9, Cytochrome C, Bax, and Bcl2. Finally, docking studies show the relevance of the free amino group of the quinoline moiety for antiproliferative action via hydrogen bond formation with essential amino acids

Aiming at the Global Elimination of Viral Hepatitis: Challenges along the Care Continuum

A recent international workshop, organised by the authors, analysed the obstacles facing the ambitious goal of eliminating viral hepatitis globally. We identified several policy areas critical to reaching elimination targets. These include: providing hepatitis B birth-dose vaccination to all infants within 24 hours of birth; preventing the transmission of blood-borne viruses through the expansion of national haemovigilance schemes; implementing the lessons learnt from the HIV epidemic regarding safe medical practices to eliminate iatrogenic infection; adopting point-of-care testing to improve coverage of diagnosis; and providing free or affordable hepatitis C treatment to all. We introduce Egypt as a case study for rapid testing and treatment scale-up: this country offers valuable insights to policy makers internationally, not only regarding how hepatitis C interventions can be expeditiously scaled-up, but also as a guide for how to tackle the problems encountered with such ambitious testing and treatment programmes