Synthesis of 1,4 Dihydropyridines as potential antimalarial chemotype

Mvumvu, Nomakhwezi

Synthesis of 1,4 Dihydropyridines as potential antimalarial chemotype

Master Thesis

2015

Publisher

University of Cape Town

Department

Department of Chemistry

Faculty

Faculty of Science

Abstract

The blood stage of the malarial parasite life-cycle is a vital stage that is believed to be a target for most antimalarial drugs. It is in this stage that host haemoglobin is degraded to provide nutrients for the survival of the parasite. However, a pathway (known as the haem detoxification pathway) that gives rise to the unique, microcrystalline ferriprotoporphryin IX [Fe(III)PPIX] dimer called haemozoin as an end-product, also arises as a result of the degradation. This haem detoxification pathway is a principal target for some of these antimalarials, especially those that contain the quinoline scaffold (e.g chloroquine), and has yielded outstanding results for the antimalarial drug discovery and development world. Even so, the spread of parasite resistance among these drugs has rendered most ineffective, resulting in a need for new scaffolds to target the pathway. However, the mode of action of chloroquine on haem may still be used as a model for identification of hits from these new scaffolds.

Keywords

Chemistry

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