Characterisation of synthetic beta-haematin and effects of the antimalarial drugs quinidine, halofantrine, desbutylhalofantrine and mefloquine on its formation.
Infrared spectroscopy, elemental analysis and X-ray powder diffraction show that the product of 30 min of reaction of haematin in 4.5 M acetate, pH 4.5 at 60 degrees C is identical to beta-haematin prepared in 4.5 M acetic acid at 70 degrees C overnight (pH 2.6). There is no evidence for formation of haem-acetate complex, which could not be isolated, even from 11.4 M acetate solution. The antimalarial drugs quinidine, halofantrine, desbutylhalofantrine and mefloquine were found to inhibit formation of beta-haematin, while 5-, 6- and 8-aminoquinoline and quinoline were found to have no effect. Quinidine was shown to form a complex with ferriprotoporphyrin IX in 40% DMSO with log K = 5.02 +/- 0.03. Log K values for halofantrine and desbutylhalofantrine are 5.29 +/- 0.02 and 5.15 +/- 0.02 respectively (solutions containing 30% acetonitrile in addition to DMSO to solubilise these drugs), which are both stronger than chloroquine under the same conditions (log K = 4.56 +/- 0.02).
Egan
T J
TJ
Department of Chemistry, University of Cape Town, Rondebosch, South Africa. tegan@psipsy.uct.ac.za
Hempelmann
E
E
Mavuso
W W
WW
D000962:Antimalarials / Q000737:chemistry*; D006427:Hemin / Q000138:chemical synthesis / Q000737:chemistry*; D015767:Mefloquine / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D010616:Phenanthrenes / Q000737:chemistry; D011802:Quinidine / Q000737:chemistry; D013055:Spectrophotometry, Infrared; D014961:X-Ray Diffraction
D000962:Antimalarials; D010616:Phenanthrenes; D006427:Hemin; C044961:1,3-dichloro-6-trifluoromethyl-9-phenanthryl-3-(n-butyl)aminopropanol; D011802:Quinidine; C023768:halofantrine; D015767:Mefloquine