3-(6-Bromo-4-oxo-4H-chromen-3-yl)-3,4-dihydro-2H-1,2,4-benzothia­diazine-1,1-dione

The mol­ecular structure of the title compound, C16H11BrN2O4S, is very similar to that of the previously reported fluoro analogue [al-Rashida et al. (2010 ▶). Acta Cryst. E66, o2707]. The mean planes of the bicyclic chromone system and the benzene ring of the benzothia­diazine derivative make a dihedral angle of 58.23 (8)°. An intra­molecular N—H⋯O hydrogen bond occurs. In the crystal, mol­ecules are linked into layers by N—H⋯O and C—H⋯O hydrogen bonds, generating an infinite two-dimensional network

4-[(Z)-(2-Eth­oxy-4-oxochroman-3-yl­idene)methyl­amino]benzene­sulfonamide monohydrate

In the mol­ecule of the title compound, C18H18N2O5S·H2O, the heterocyclic ring adopts a twisted conformation, while the aromatic rings are oriented at a dihedral angle of 45.46 (3)°. Intra­molecular C—H⋯O and N—H⋯O inter­actions result in the formations of planar five- and six-membered rings. In the crystal structure, N—H⋯O hydrogen bonds link the NH2 and SO2 groups through R 2 2(8) ring motifs, while C—H⋯O and N—H⋯O hydrogen bonds result in the formation of R 2 1(7) ring motifs. N—H⋯O and O—H⋯O hydrogen bonds link the uncoordinated water mol­ecules, forming a polymeric network. A weak C—H⋯π inter­action is also present

3-(6-Fluoro-4-oxo-4H-chromen-3-yl)-3,4-dihydro-2H-1,2,4-benzothia­diazine-1,1-dione

In the title compound, C16H11FN2O4S, the mean planes of the bicyclic chromone system and of the benzene ring of the benzothia­diazine derivative make a dihedral angle of 54.28 (5)°. An intra­molecular N—H⋯O hydrogen bond occurs. In the crystal, mol­ecules are linked into layers by N—H⋯O and C—H⋯O hydrogen bonds, generating an infinite two-dimensional network

Novel acridine-based thiosemicarbazones as ‘turn-on' chemosensors for selective recognition of fluoride anion: a spectroscopic and theoretical study

New thiosemicarbazide-linked acridines 3a–c were prepared and investigated as chemosensors for the detection of biologically and environmentally important anions. The compounds 3a–c were found selective for fluoride (F−) with no affinity for other anions, i.e. −OAc, Br−, I−, HSO4−, SO42−, PO43−, ClO3−, ClO4−, CN− and SCN−. Further, upon the gradual addition of a fluoride anion (F−) source (tetrabutylammonium fluoride), a well-defined change in colour of the solution of probes 3a–c was observed. The anion-sensing process was studied in detail via UV–visible absorption, fluorescence and 1H-NMR experiments. Moreover, during the synthesis of acridine probes 3a–c nickel fluoride (NiF2), a rarely explored transition metal fluoride salt, was used as the catalyst. Theoretical studies via density functional theory were also carried out to further investigate the sensing and anion (F−) selectivity pattern of these probes

Pyrazole derivatives of pyridine and naphthyridine as proapoptotic agents in cervical and breast cancer cells

Cancer is one of the leading causes of death worldwide. The increasing prevalence and resistance to chemotherapy is responsible for driving the search of novel molecules to combat this disease. In search of novel compounds with pro-apoptotic potential, pyrazolo-pyridine and pyrazolo-naphthyridine derivatives were investigated against cervical cancer (HeLa) and breast cancer (MCF-7) cells. The anti-proliferative activity was determined through the MTT assay. Potent compounds were then analyzed for their cytotoxic and apoptotic activity through a lactate dehydrogenase assay and fluorescence microscopy after propidium iodide and DAPI staining. Flow cytometry was used to determine cell cycle arrest in treated cells and pro-apoptotic effect was verified through measurement of mitochondrial membrane potential and activation of caspases. Compounds 5j and 5k were found to be most active against HeLa and MCF-7 cells, respectively. G0/G1 cell cycle arrest was observed in treated cancer cells. Morphological features of apoptosis were also confirmed, and an increased oxidative stress indicated the involvement of reactive oxygen species in apoptosis. The compound-DNA interaction studies demonstrated an intercalative mode of binding and the comet assay confirmed the DNA damaging effects. Finally, potent compounds demonstrated a decrease in mitochondrial membrane potential and increased levels of activated caspase-9 and -3/7 confirmed the induction of apoptosis in treated HeLa and MCF-7 cells. The present work concludes that the active compounds 5j and 5k may be used as lead candidates for the development of lead drug molecules against cervical and breast cancer

THE ROLE OF THE GEOPOLITICAL POSITION OF THE HASHEMITE KINGDOM OF JORDAN TOWARDS AMERICAN FOREIGN POLICY FROM 1990 TO 2017

The role of the geopolitical location of the Hashemite Kingdom of Jordan towards United States (US) foreign policy from 1990 to 2017 is the focus of this study, which addressed the impact of important regional and international political events, positively or negatively, on the development of relations between the two countries in terms of political and security aspects. The study adopted a qualitative approach, and primary data was collected through interviews with 16 participants from political, economic, and security experts in Jordan and the US. Thematic analysis was used to analyze the data obtained. The study concluded that US foreign policy recognizes Jordan as a close ally and considers its stability extremely important; Jordan has a suitable location to defend Israel because critical Arab countries surround it, and Jordan enjoys a unique geographical location in the Middle East. Some political events play an essential role in US foreign policy concerning security aid to Jordan, as the US links its aid to Jordan to political events.

A Research Agenda for Helminth Diseases of Humans: Diagnostics for Control and Elimination Programmes

Diagnostic tools appropriate for undertaking interventions to control helminth infections are key to their success. Many diagnostic tests for helminth infection have unsatisfactory performance characteristics and are not well suited for use in the parasite control programmes that are being increasingly implemented. Although the application of modern laboratory research techniques to improve diagnostics for helminth infection has resulted in some technical advances, uptake has not been uniform. Frequently, pilot or proof of concept studies of promising diagnostic technologies have not been followed by much needed product development, and in many settings diagnosis continues to rely on insensitive and unsatisfactory parasitological or serodiagnostic techniques. In contrast, PCR-based xenomonitoring of arthropod vectors, and use of parasite recombinant proteins as reagents for serodiagnostic tests, have resulted in critical advances in the control of specific helminth parasites. The Disease Reference Group on Helminths Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR) was given the mandate to review helminthiases research and identify research priorities and gaps. In this review, the diagnostic technologies relevant to control of helminth infections, either available or in development, are reviewed. Critical gaps are identified and opportunities to improve needed technologies are discussed

Identification and characterization of antibacterial compound(s) of cockroaches (Periplaneta americana)

Infectious diseases remain a significant threat to human health, contributing to more than 17 million deaths, annually. With the worsening trends of drug resistance, there is a need for newer and more powerful antimicrobial agents. We hypothesized that animals living in polluted environments are potential source of antimicrobials. Under polluted milieus, organisms such as cockroaches encounter different types of microbes, including superbugs. Such creatures survive the onslaught of superbugs and are able to ward off disease by producing antimicrobial substances. Here, we characterized antibacterial properties in extracts of various body organs of cockroaches (Periplaneta americana) and showed potent antibacterial activity in crude brain extract against methicillin-resistant Staphylococcus aureus and neuropathogenic E. coli K1. The size-exclusion spin columns revealed that the active compound(s) are less than 10 kDa in molecular mass. Using cytotoxicity assays, it was observed that pre-treatment of bacteria with lysates inhibited bacteria-mediated host cell cytotoxicity. Using spectra obtained with LC-MS on Agilent 1290 infinity liquid chromatograph, coupled with an Agilent 6460 triple quadruple mass spectrometer, tissues lysates were analyzed. Among hundreds of compounds, only a few homologous compounds were identified that contained isoquinoline group, chromene derivatives, thiazine groups, imidazoles, pyrrole containing analogs, sulfonamides, furanones, flavanones, and known to possess broad-spectrum antimicrobial properties, and possess anti-inflammatory, anti-tumour, and analgesic properties. Further identification, characterization and functional studies using individual compounds can act as a breakthrough in developing novel therapeutics against various pathogens including superbugs

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life