Molecular modeling studies of the artemisinin (qinghaosu)-hemin interaction: docking between the antimalarial agent and its putative receptor.
Artemisinin (qinghaosu, QHS) is a promising new antimalarial agent that is effective against drug-resistant strains of malaria. The antimalarial activity of this drug appears to be mediated by an interaction of the drug's endoperoxide bridge with intraparasitic hemin. We have carried out a computer-assisted docking of QHS with hemin from various starting configurations and found that, in the most stable docked configuration, the endoperoxide bridge is in close proximity to the hemin iron. In contrast, an inactive analog, deoxyartemisinin (DQHS), docks in a different manner. Further computer analysis of the drug-hemin interaction might aid in the design of new QHS congeners.
Shukla
K L
KL
Department of Chemistry and Chemical Engineering, New Jersey Institute of Technology, Newark 07102, USA.
Gund
T M
TM
Meshnick
S R
SR
D000962:Antimalarials / Q000737:chemistry* / Q000378:metabolism; D037621:Artemisinins; D003198:Computer Simulation; D015195:Drug Design; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D006427:Hemin / Q000737:chemistry* / Q000378:metabolism; D007501:Iron / Q000737:chemistry; D008958:Models, Molecular; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism; D012717:Sesquiterpenes / Q000737:chemistry* / Q000378:metabolism
D000962:Antimalarials; D037621:Artemisinins; D004365:Drugs, Chinese Herbal; D018160:Receptors, Cytoplasmic and Nuclear; D012717:Sesquiterpenes; C055261:deoxyartemisinin; D006427:Hemin; C031327:artemisinin; D007501:Iron