2-Aryl-6,8-dibromo-2,3-dihydroquinazolin-4(1H)-ones as substrates for the synthesis of 2,6,8-triarylquinazolin-4-ones

Direct bromination of 2-aminobenzamide was achieved using N-bromosuccinimide in chloroform-carbon tetrachloride mixture at room temperature for 3 h to afford 2-amino-3,5-dibromobenzamide in high yield and purity. 2-Amino-3,5-dibromobenzamide was, in turn, condensed with benzaldehyde derivatives in the presence of boric acid to afford novel 2-aryl-6,8-dibromo-2,3-dihydroquinazolin-4(1H)-ones. Suzuki-Miyaura cross-coupling of the latter with arylboronic acids yielded the corresponding 2,6,8-triaryl-2,3-dihydroquinazolin-4(1H)-ones. These triarylquinazolin-4(1H)-ones were dehydrogenated using iodine (2 equiv.) in ethanol under reflux to yield the potentially tautomeric 2,6,8-triarylquinazolin-4(3H)-ones. KEY WORDS: 2-Amino-3,5-dibromobenzamide, 2-Aryl-6,8-dibromo-2,3-dihydroquinazolin-4(1H)-ones, Suzuki-Miyaura cross-coupling, 2,6,8-Triaryl-2,3-dihydroquinazolin-4(1H)-ones, 2,6,8-Triarylquinazolin-4(3H)-ones Bull. Chem. Soc. Ethiop. 2014, 28(1), 81-90.   DOI: http://dx.doi.org/10.4314/bcse.v28i1.1

Using microscience kits to address a student-teacher misconception in electric circuits: At the interface between chemistry and electricity

A test of education students’ understanding of electric circuits, written before their lectures on the topic began, led to practical work with micro-scale circuit apparatus that was designed to further probe and challenge the students’ misconceptions. Response data from one of the lab pracs revealed one very common misconception, that the current through a component was the cause of the potential difference across it. A practical activity based upon the Volta pile was designed to show that current is not the cause of voltage, and that voltage is to be traced to the chemical reaction inside the cells. While some aspects of the activity were successful in a workshop at 10th ISMC, others were not. Our reflections on the outcome lead us to the conclusion that it is necessary to engage with the chemical events inside the cell, in order to understand how it works. Systems-thinking may be the way forward

Synthesis and Evaluation of N-(3-Trifluoroacetylindol- 7-yl) Acetamides for Potential In Vitro Antiplasmodial Properties

A series of novel N-((2,5-diaryl-3-trifluoroacetyl)-1H-indol-7-yl)acetamides has been prepared via a successive and one-pot reaction sequence involving initial trifluoroacetic acid-mediated Beckmann rearrangement of the oximes derived from the 1-(2,5-diaryl-1H-indol-7-yl)ethanones, followed by trifluoroacetylation of the incipient N-(2,5-diaryl-1H-indol-7-yl)-acetamides with trifluoroacetic anhydride. The prepared compounds were evaluated for potential in vitro antiplasmodial properties. Preliminary results from antiplasmodial activity against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum revealed that a combination of 2-(4-flurophenyl)- and 5-(4-fluorophenyl) or 2-(4-flurophenyl)- and 4-fluorostyryl groups in compounds 3(a,f) and 4(a,g), for example, is required for biological activity for both series of compounds. Their possible mode of action against the plasmodial parasite is explained theoretically through molecular docking of the most active compounds against the parasite lactate dehydrogenase (pLDH). These compounds were docked at the entrance of NAD+ in pLDH presumably hindering entry of lactate to cause the observed inhibition effect of pLDH. The four compounds were found to exhibit low toxicity against monkey kidney Vero cells at the highest concentrations tested

Maternal effects on phenotype, resistance and the structuring of fungal communities in Eucalyptus grandis

The environmental experience of plants can modulate the development of the offspring and their interactions with other organisms. These effects, generally known as maternal effects, occur through seed provisioning and epigenetic modifications. This study considers the influence of differing environments of maternal plants on their progeny and their biotic interactions. Seeds were collected from two Eucalyptus grandis clonal seed orchards having different abiotic and biotic conditions. Seed and seedling development, and seedling responses to pest infestation and pathogen inoculation were measured. Finally, fungal communities in the foliage of the seedlings were assessed using a metabarcoding approach. The percentage of seed germination and height of seedlings were influenced by the maternal environments. Seedlings from one of the maternal environments were significantly more resistant to a pathogen than seedlings from the other. The composition and diversity of fungal communities also differed between the offspring from the two maternal environments. We found that the differences in the maternal environment affected the progeny performance and resistance. Moreover, we show for the first time that the maternal environment can influence the structure of fungal communities in the foliage in the subsequent generation.The Claude Leon Foundation, University of Pretoria, the Tree Protection Co-operative Programme, and the Genome Research Institute at the University of Pretoria.http://www.elsevier.com/locate/envexpbot2018-08-30hj2017Forestry and Agricultural Biotechnology Institute (FABI)GeneticsMicrobiology and Plant Patholog

Variability of the preC/C region of hepatitis B virus genotype A from a South African cohort predominantly infected with HIV

Hepatitis B virus (HBV) is a serious global health problem, and HBV genotype is an important determinant of disease progression and treatment outcome. The aim of this study was to assess variations of the precore/core (preC/C) region in HBV genotype A. Sequencing of the preC/C and surface (S) genes of HBV was performed on plasma samples from 20 HBV/HIV co-infected and 5 HBV mono-infected individuals. All preC/C study sequences clustered with subgenotype A1, except for two which clustered with subgenotype D4 reference strains. The nucleotide and amino acid variability was far higher in the preC/C region than in the S region. Mutations associated with reduction or failure of HBV e-antigen (HBeAg) production were observed, with a preC start codon mutation being common (24%). Other mutations (e.g., P5H/L and I97L) associated with severe liver disease were also noticed, some of which were located in the major histocompatibility restricted sites. PreC/C intergenotype nucleotide divergence was >7%, while subgenotypes differed by 2.5–7%. Several study sequences were highly divergent from other African subgenotype A1 strains. This study showed that HBeAg-negative chronic hepatitis B is underestimated in subgenotype A1, and also highlighted the variant South African A1 strains. The major advantage of preC/C sequencing is that it informs patient management as HBeAg-negative chronic hepatitis B responds poorly to conventional interferon-α therapy, and some guidelines treat HBeAg-negative chronic hepatitis B differently from HBeAg-positive chronic hepatitis B. These data suggest that subgenotype A1 may be more involved in severe HBV-related diseaseshttp://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1096-9071/hb201

HBV/HIV co-infection: The dynamics of HBV in South African patients with AIDS

Objective. As sub-Saharan Africa is highly endemic for hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections, and their co-infection requires special management, we aimed to assess the serological and molecular characteristics of HBV in patients with AIDS. Design. This was a cross-sectional, case control study, which enrolled 200 patients with AIDS and 200 HIV-negative controls. HBV serology was done in all participants and HCV serology in participants with a hepatitis B core antibody (anti-HBc) only serological pattern. Nested HBV polymerase chain reaction (PCR) and HBV viral load assays were used for HBV molecular detection. Results. Hepatitis B surface antigen (HBsAg) prevalence was 3-fold higher while the ‘anti-HBc only’ pattern was 6-fold higher in the AIDS group compared with the controls. Mean HBV viral load was significantly higher in HBsAg-positive patients with CD4+ cell count

Variability of the preC/C region of hepatitis B virus genotype A from a South African cohort predominantly infected with HIV

ABSTRACT Hepatitis B virus (HBV) is a serious global health problem, and HBV genotype is an important determinant of disease progression and treatment outcome. The aim of this study was to assess variations of the precore/core (preC/C) region in HBV genotype A. Sequencing of the preC/C and surface (S) genes of HBV was performed on plasma samples from 20 HBV/HIV co-infected and 5 HBV mono-infected individuals. All preC/C study sequences clustered with subgenotype A1, except for 2 which clustered with subgenotype D4 reference strains. The nucleotide and amino acid variability was far higher in the preC/C region than in the S region. Mutations associated with reduction or failure of HBV e-antigen (HBeAg) production were observed, with a preC start codon mutation being common (24%). Other mutations (e.g. P5H/L and I97L) associated with severe liver disease were also noticed, some of which were located in the major histocompatibility restricted sites. PreC/C intergenotype nucleotide divergence was >7%, while subgenotypes differed by 2.5 -7%. Several study sequences were highly divergent from other African subgenotype A1 strains. This study showed that HBeAg-negative chronic hepatitis B is underestimated in subgenotype A1, and also highlighted the variant South African A1 strains. The major advantage of preC/C sequencing is that it informs patient management as HBeAgnegative chronic hepatitis B responds poorly to conventional interferon-α therapy, and some guidelines treat HBeAg-negative chronic hepatitis B differently from HBeAg-positive chronic hepatitis B. These data suggest that subgenotype A1 may be more involved in severe HBVrelated diseases

Impact of lamivudine-based antiretroviral treatment on hepatitis B viremia in HIV-coinfected South Africans

This prospective study investigated the impact of lamivudine-containing antiretroviral therapy (ART) on HIV-positive patients in South Africa with baseline hepatitis B virus (HBV) infection. Follow-up samples from 56 HBV/HIV co-infected patients, 25 with occult HBV infection (OBI) and 31 with chronic HBV infection (CHB), were available for analysis. HBV viral loads were quantified at 6, 12, 18, and 24 months post-ART initiation by the COBAS TaqMan HBV Test 48 assay, and the HBV polymerase gene was amplified with an in-house nested polymerase chain reaction assay. During 24 months of lamivudine-based ART, 6 of 8 (75%) OBI and 4 of 6 (67%) CHB patients achieved undetectable levels of HBV DNA, while 2 patients had persistent HBV DNA levels 2 105 despite lamivudine-based ART for 24 months. HIV viremia was undetectable in all patients at 12 months, suggesting high adherence to ART. Several lamivudine-associated HBV resistance mutations, including L180M, A181T, M204I, and M204V, were observed. Sequence analysis also revealed a rare genotype G infection. While resource-limited settings may use lamivudine-based ART because of availability and low cost, antivirals with dual therapy against HBV and HIV (e.g., lamivudine and tenofovir) should always be recommended with the regular monitoring of HBV viremia levels.The South African National Research Foundation, Poliomyelitis Research Foundation, Stella and Paul Lowenstein Trust, and Canon and Collins scholarship.http://www.mdpi.com/journal/virusesam2021Medical Virolog