Molecular modeling studies of the artemisinin (qinghaosu)-hemin interaction: Docking between the antimalarial agent and its putative receptor

Kanhiya L. Shukla; Tamara M. Gund; Steven R. Meshnick

doi:10.1016/0263-7855(94)00001-9

Molecular modeling studies of the artemisinin (qinghaosu)-hemin interaction: Docking between the antimalarial agent and its putative receptor

Kanhiya L. Shukla, Tamara M. Gund, Steven R. Meshnick

Chemistry and Environmental Science

Research output: Contribution to journal › Article › peer-review

57 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	215-222
Number of pages	8
Journal	Journal of Molecular Graphics
Volume	13
Issue number	4
DOIs	https://doi.org/10.1016/0263-7855(94)00001-9
State	Published - Aug 1995

All Science Journal Classification (ASJC) codes

Biophysics
Biochemistry

Keywords

antimalarial
artemisinin
docking
hemin
malaria
molecular modeling
qinghaosu

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10.1016/0263-7855(94)00001-9

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title = "Molecular modeling studies of the artemisinin (qinghaosu)-hemin interaction: Docking between the antimalarial agent and its putative receptor",

abstract = "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.",

keywords = "antimalarial, artemisinin, docking, hemin, malaria, molecular modeling, qinghaosu",

author = "Shukla, {Kanhiya L.} and Gund, {Tamara M.} and Meshnick, {Steven R.}",

note = "Funding Information: This work was supported by NIH Grant AI26848 and by a grant from the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases.",

year = "1995",

month = aug,

doi = "10.1016/0263-7855(94)00001-9",

language = "English (US)",

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journal = "Journal of Molecular Graphics",

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T2 - Docking between the antimalarial agent and its putative receptor

AU - Shukla, Kanhiya L.

AU - Gund, Tamara M.

AU - Meshnick, Steven R.

N1 - Funding Information: This work was supported by NIH Grant AI26848 and by a grant from the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases.

PY - 1995/8

Y1 - 1995/8

N2 - 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.

AB - 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.

KW - antimalarial

KW - artemisinin

KW - docking

KW - hemin

KW - malaria

KW - molecular modeling

KW - qinghaosu

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JF - Journal of Molecular Graphics

IS - 4

ER -

Molecular modeling studies of the artemisinin (qinghaosu)-hemin interaction: Docking between the antimalarial agent and its putative receptor

Abstract

All Science Journal Classification (ASJC) codes

Keywords

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