Screening of the Pan-African Natural Product Library Identifies Ixoratannin A-2 and Boldine as Novel HIV-1 Inhibitors

The continued burden of HIV in resource-limited regions such as parts of sub-Saharan Africa, combined with adverse effects and potential risks of resistance to existing antiretroviral therapies, emphasize the need to identify new HIV inhibitors. Here we performed a virtual screen of molecules from the pan-African Natural Product Library, the largest collection of medicinal plant-derived pure compounds on the African continent. We identified eight molecules with structural similarity to reported interactors of Vpu, an HIV-1 accessory protein with reported ion channel activity. Using in vitro HIV-1 replication assays with a CD4+ T cell line and peripheral blood mononuclear cells, we confirmed antiviral activity and minimal cytotoxicity for two compounds, ixoratannin A-2 and boldine. Notably, ixoratannin A-2 retained inhibitory activity against recombinant HIV-1 strains encoding patient-derived mutations that confer resistance to protease, non-nucleoside reverse transcriptase, or integrase inhibitors. Moreover, ixoratannin A-2 was less effective at inhibiting replication of HIV-1 lacking Vpu, supporting this protein as a possible direct or indirect target. In contrast, boldine was less effective against a protease inhibitor-resistant HIV-1 strain. Both ixoratannin A-2 and boldine also inhibited in vitro replication of hepatitis C virus (HCV). However, BIT-225, a previously-reported Vpu inhibitor, demonstrated antiviral activity but also cytotoxicity in HIV-1 and HCV replication assays. Our work identifies pure compounds derived from African plants with potential novel activities against viruses that disproportionately afflict resource-limited regions of the world

Residents' perceptions of the Berg River canoe marathon as a major sporting event in the Western Cape

Thesis (MTech (Tourism and Hospitality Management))--Cape Peninsula University of Technology, 2006This research examines the ways in which local residents living in close proximity to the event perceived the Berg River Canoe Marathon as a major event in the Western Cape. By identif'ying these different patterns ofperceptions within the community, it is possible to gain a better understanding of both the tangible and intangible impacts of events and how they differently affect the quality of life of local residents as individuals and the community as a whole. The research method was based on a convenient sampling approach. A questionnaire survey of two hundred residents was conducted and five different dimensions of perceiving the impacts of events were examined ranging from extremely negative to very positive. The impacts analysed included social, economic and environmental impacts. The residents in all the five locations perceived community pride and entertainment to be very positive and were in favour ofthe continuation of the event. 1n profiling the residents who held each of the representations identified, it was found that the most negative group was those residents who had little or no involvement in tourism and are not interested in canoeing as a sport. Thus, it is necessary for event organisers and event managers to get the members of community involved in the planning and management of the event to spread the benefits to a larger portion of the community

<b>Reaction of propargyltrimethylsilane magnesium bromide with aldimines: Synthesis of 1-(alkylamino)-2-(trimethylsilyl)but-3-yne</b>

The reaction of propargylsilane magnesium bromide with aldimines provides in some cases, an isomeric mixture of three acetylenic amines <b>1</b>, <b>2</b>, <b>3</b> (<b>1</b> and <b>2</b>, as major products). The reaction has great potential and has been exploited for an efficient synthesis of the pure amine <b>2</b>

Pharmacophore modeling and in silico toxicity assessment of potential anticancer agents from African medicinal plants

Fidele Ntie-Kang,1,2,* Conrad Veranso Simoben,1,2,* Berin Karaman,1 Valery Fuh Ngwa,3 Philip Neville Judson,4 Wolfgang Sippl,1 Luc Meva&rsquo;a Mbaze5 1Department of Pharmaceutical Chemistry, Martin-Luther University of Halle-Wittenberg, Halle (Saale), Germany; 2Department of Chemistry, University of Buea, Buea, Cameroon; 3Interuniversity Institute For Biostatistics and Statistical Bioinformatics (I-BioStat), University of Hasselt, Hasselt, Belgium; 4Chemical Bioactivity Information Centre, Harrogate, UK; 5Department of Chemistry, Faculty of Science, University of Douala, Douala, Cameroon *These authors contributed equally to this work Abstract: Molecular modeling has been employed in the search for lead compounds of chemotherapy to fight cancer. In this study, pharmacophore models have been generated and validated for use in virtual screening protocols for eight known anticancer drug targets, including tyrosine kinase, protein kinase B &beta;, cyclin-dependent kinase, protein farnesyltransferase, human protein kinase, glycogen synthase kinase, and indoleamine 2,3-dioxygenase 1. Pharmacophore models were validated through receiver operating characteristic and G&uuml;ner&ndash;Henry scoring methods, indicating that several of the models generated could be useful for the identification of potential anticancer agents from natural product databases. The validated pharmacophore models were used as three-dimensional search queries for virtual screening of the newly developed AfroCancer database (~400 compounds from African medicinal plants), along with the Naturally Occurring Plant-based Anticancer Compound-Activity-Target dataset (comprising ~1,500 published naturally occurring plant-based compounds from around the world). Additionally, an in silico assessment of toxicity of the two datasets was carried out by the use of 88 toxicity end points predicted by the Lhasa&rsquo;s expert knowledge-based system (Derek), showing that only an insignificant proportion of the promising anticancer agents would be likely showing high toxicity profiles. A diversity study of the two datasets, carried out using the analysis of principal components from the most important physicochemical properties often used to access drug-likeness of compound datasets, showed that the two datasets do not occupy the same chemical space. Keywords: anticancer, natural products, medicinal plants, pharmacophore, toxicity, virtual screenin

Acridone Alkaloids and Coumarins from the Stem Bark of Citropsis articulata (Rutaceae)

Meva'a LM, Songue JL, Wansi J, et al. Acridone Alkaloids and Coumarins from the Stem Bark of Citropsis articulata (Rutaceae). Zeitschrift für Naturforschung B. 2010;65(4):525-527.A new acridone alkaloid, citropsine A (1), and thirteen known compounds (2-14) were isolated from the MeOH extract of the stem bark of Citropsis articulata. Structures of all compounds were determined by detailed analyses of their ID and 2D NMR spectra, mass spectrometric data and by comparison with previously known analogs

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The potential of anti-malarial compounds derived from African medicinal plants. Part I: A pharmacological evaluation of alkaloids and terpenoids Amoa Onguéné et al