Facile oxidation of leucomethylene blue and dihydroflavins by artemisinins: relationship with flavoenzyme function and antimalarial mechanism of action

…, ID Williams, D Prosperi, S Melato, P Coghi…

Index: Haynes, Richard K.; Chan, Wing-Chi; Wong, Ho-Ning; Li, Ka-Yan; Wu, Wai-Keung; Fan, Kit-Man; Sung, Herman H. Y.; Williams, Ian D.; Prosperi, Davide; Melato, Sergio; Coghi, Paolo; Monti, Diego ChemMedChem, 2010 , vol. 5, # 8 p. 1282 - 1299

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Citation Number: 50

Abstract

Abstract The antimalarial drug methylene blue (MB) affects the redox behaviour of parasite flavin-dependent disulfide reductases such as glutathione reductase (GR) that control oxidative stress in the malaria parasite. The reduced flavin adenine dinucleotide cofactor FADH 2 initiates reduction to leucomethylene blue (LMB), which is oxidised by oxygen to generate reactive oxygen species (ROS) and MB. MB then acts as a subversive substrate ...