Iron(III) protoporphyrin IX complexes of the antimalarial cinchona alkaloids quinine and quinidine

Simple item page
dc.contributor.authorDe Villiers K.A.
dc.contributor.authorGildenhuys J.
dc.contributor.authorLe Roex T.
dc.date.accessioned2012-06-06T07:53:35Z
dc.date.available2012-06-06T07:53:35Z
dc.date.issued2012
dc.description.abstractThe antimalarial properties of the Cinchona alkaloids quinine and quinidine have been known for decades. Surprisingly, 9-epiquinine and 9-epiquinidine are almost inactive. A lack of definitive structural information has precluded a clear understanding of the relationship between molecular structure and biological activity. In the current study, we have determined by single crystal X-ray diffraction the structures of the complexes formed between quinine and quinidine and iron(III) protoporphyrin IX (Fe(III)PPIX). Coordination of the alkaloid to the Fe(III) center is a key feature of both complexes, and further stability is provided by an intramolecular hydrogen bond formed between a propionate side chain of Fe(III)PPIX and the protonated quinuclidine nitrogen atom of either alkaloid. These interactions are believed to be responsible for inhibiting the incorporation of Fe(III)PPIX into crystalline hemozoin during its in vivo detoxification. It is also possible to rationalize the greater activity of quinidine compared to that of quinine. © 2012 American Chemical Society.
dc.identifier.citationACS Chemical Biology
dc.identifier.citation7
dc.identifier.citation4
dc.identifier.citation666
dc.identifier.citation671
dc.identifier.issn15548929
dc.identifier.otherdoi:10.1021/cb200528z
dc.identifier.urihttp://hdl.handle.net/10019.1/21230
dc.titleIron(III) protoporphyrin IX complexes of the antimalarial cinchona alkaloids quinine and quinidine
dc.typeReview
Files
Collections
Stellenbosch University - Scopus Publications