Browsing by Author "Amewu, R."
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Item Making North–South Collaborations Work: Facilitating Natural Product Drug Discovery in Africa(Springer link, 2019) Osei-Safo, D.; Kyeremeh, K.; Amewu, R.; et al.Many global North–South collaborations seek to address different aspects of the Sustainable Development Goals (SDGs) for Africa . The role of the North in these collaborations is crucial from a funding point of view. However, the realisation of the SDG objectives for Africa will depend largely on strategies that are guided by the successes and challenges of previous and existing collaborative efforts. Globally, Africa has the highest disease burden with the leading causes of morbidity and mortality being malaria, tuberculosis, HIV and AIDS and more recently, cardiovascular diseases , diabetes and cancer. Neglected tropical diseases are also causing long-term detrimental health effects, resulting in huge social and economic losses. Ironically, the continent is endowed with a huge biodiversity resource that has the potential to provide novel and potent drug candidates but remains largely unexplored partly due to financial and infrastructural challenges. Developing the scientific research capabilities of African institutions towards drug discovery through global networks is, therefore, an important component of improving health systems on the continent. This chapter examines experiences from three North–South collaborations—the Royal Society’s Leverhulme Trust Africa Award (LTAA), Newton Advanced Fellowships (NAF) and Cambridge-Africa Partnership for Research Excellence (CAPREx)—and proposes the adoption of structures that extend the current focus on skill transfer to include the building and maintenance of sustainable infrastructure. It is believed that these thoughts and suggestions could promote sustainable collaborative research to provide good health and well-being (SDG3), quality education (SDG4), relevant infrastructure (SDG9) and reduced inequalities (SDG10) in Africa .Item Rational Design, Synthesis, and Biological Evaluation of Heterocyclic Quinolones Targeting the Respiratory Chain of Mycobacterium tuberculosis(Journal of Medicinal Chemistry, 2017) Hong, W.D.; Gibbons, P.D.; Leung, S.C.; Amewu, R.; Stocks, P.A.; Stachulski, A.; Horta, P.; Cristiano, M.L.S.; Shone, A.E.; Moss, D.; Ardrey, A.; Sharma, R.; Warman, A.J.; Bedingfield, P.T.P.; Fisher, N.E.; Aljayyoussi, G.; Mead, S.; Caws, M.; Berry, N.G.; Ward, S.A.; Biagini, G.A.; O’Neill, P.M.; Nixon, G.L.A high-throughput screen (HTS) was undertaken against the respiratory chain dehydrogenase component, NADH:menaquinone oxidoreductase (Ndh) of Mycobacterium tuberculosis (Mtb). The 11000 compounds were selected for the HTS based on the known phenothiazine Ndh inhibitors, trifluoperazine and thioridazine. Combined HTS (11000 compounds) and in-house screening of a limited number of quinolones (50 compounds) identified ∼100 hits and four distinct chemotypes, the most promising of which contained the quinolone core. Subsequent Mtb screening of the complete in-house quinolone library (350 compounds) identified a further ∼90 hits across three quinolone subtemplates. Quinolones containing the amine-based side chain were selected as the pharmacophore for further modification, resulting in metabolically stable quinolones effective against multi drug resistant (MDR) Mtb. The lead compound, 42a (MTC420), displays acceptable antituberculosis activity (Mtb IC 50 = 525 nM, Mtb Wayne IC 50 = 76 nM, and MDR Mtb patient isolates IC 50 = 140 nM) and favorable pharmacokinetic and toxicological profiles. © 2017 American Chemical Society.