The novel antimalarial compound dioncophylline C forms a complex with heme in solution.

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Schwedhelm KF, Horstmann M, Faber JH, Reichert Y, Bringmann G, Faber C

The novel antimalarial compound dioncophylline C forms a complex with heme in solution.

ChemMedChem. 2007 Apr;2(4):541-8.

PubMed ID

17315144 [ View in PubMed

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Abstract

A structural model of the complex formed between the novel antimalarial compound dioncophylline C (DioC) and its presumed target ferriprotoporphyrin IX heme (FPIX) is presented. The complex structure was calculated with molecular dynamics (MD) simulations using intermolecular distance restraints between DioC and the iron center in FPIX, determined from NMR paramagnetic relaxation. Besides the spin state of the iron and longitudinal relaxation rates of hydrogen nuclei in DioC, the effective correlation time of paramagnetic relaxation was determined from NMR measurements at three different magnetic field strengths. The derived structural model shows high similarity to complexes formed by FPIX and antimalarials of the quinoline family (chloroquine, quinine, quinidine, and amodiaquine). The conformation of DioC is sterically stabilized by a water molecule coordinated to iron in FPIX. This structural feature may provide an important hint at possibilities for a further optimization of novel naphthylisoquinoline alkaloid (NIQ) antimalarial drugs.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Amodiaquine	Fe(II)-protoporphyrin IX	Small molecule	Plasmodium falciparum	Yes	Binder	Details