Dimension of intervention for student development

xvii, 339 p.; 23 cm

Unsymmetrical Bisquinolines with High Potency against P. falciparum Malaria

Quinoline-based scaffolds have been the mainstay of antimalarial drugs, including many artemisinin combination therapies (ACTs), over the history of modern drug development. Although much progress has been made in the search for novel antimalarial scaffolds, it may be that quinolines will remain useful, especially if very potent compounds from this class are discovered. We report here the results of a structure-activity relationship (SAR) study assessing potential unsymmetrical bisquinoline antiplasmodial drug candidates using in vitro activity against intact parasites in cell culture. Many unsymmetrical bisquinolines were found to be highly potent against both chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum parasites. Further work to develop such compounds could focus on minimizing toxicities in order to find suitable candidates for clinical evaluation

Simplified Reversed Chloroquines To Overcome Malaria Resistance to Quinoline-Based Drugs

Building on our earlier work of attaching a chemosensitizer (reversal agent) to a known drug pharmacophore, we have now expanded the structure-activity relationship study to include simplified versions of the chemosensitizer. The change from two aromatic rings in this head group to a single ring does not appear to detrimentally affect the antimalarial activity of the compounds. Data from in vitro heme binding and beta-hematin inhibition assays suggest that the single aromatic RCQ compounds retain activities against Plasmodium falciparum similar to those of CQ, although other mechanisms of action may be relevant to their activities

A Scalable Solution to Constant Potential Flow Electrochemistry

The burgeoning interest in new electrochemical methods holds promise to provide a plethora of strategic disconnections for pharmaceutical compounds, which are safer, less wasteful, and more streamlined than traditional chemical strategies. The use of organic electrochemistry in the commercial production of pharmaceuticals is exceedingly rare due to the lack of a modular infrastructure. Herein, we describe the use of cascading continuous-stirred tank reactors (CSTRs) with individual cell potential control applied over reaction ‘stages’ which demonstrate a balance between high selectivity and throughput necessary for electrochemistry to be a viable strategy in the pharmaceutical space. Using the high degree of control of cell potential afforded by this reactor design, a 1 kg demonstration was achieved in 9 hours with high selectivity and yield (2.6 kg/day throughput)

Protestant Unity and Anti-Catholicism: The Irenicism and Philo-Semitism of John Dury in Context

This article examines the religious and political worldview of the Scottish minister John Dury during the English Revolution of the mid-seventeenth century. It argues that Dury's activities as an irenicist and philo-semite must be understood as interrelated aspects of an expansionist Protestant cause that included Britain, Ireland, continental Europe, and the Atlantic world. Dury sought to imitate and counter what he perceived to be the principal strengths of early modern Catholicism: confessional unity, imperial expansion, and the coordination of global missionary efforts. The 1640s and 1650s saw the scope of Dury's long-standing vision grow to encompass colonial expansion in Ireland and America, where English and continental Protestants might work together to fortify their position against Spain and its growing Catholic empire. Both Portuguese Jews and American Indians appear in this vision as victims of Spanish Catholicism in desperate need of Protestant help. This article thus offers new perspectives on several aspects of Dury's career, including his relationship with displaced Anglo-Irish Protestants in London, his proposal to establish a college for the study of Jewish learning and " Oriental " languages, his speculation regarding the Lost Tribes of Israel in America, and his cautious advocacy for the toleration of Jews in England