Characterisation of synthetic beta-haematin and effects of the antimalarial drugs quinidine, halofantrine, desbutylhalofantrine and mefloquine on itsformation

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 ac id at 70 degrees C overnight (pH 2.6). There is no evidence for formation o f haem-acetate complex, which could not be isolated, even from 11.4 M aceta te solution. The antimalarial drugs quinidine, halofantrine, desbutylhalofa ntrine and mefloquine were found to inhibit formation of beta-haematin, whi le 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% DM SO with log K = 5.02 +/- 0.03. Log K values for halofantrine and desbutylha lofantrine are 5.29 +/- 0.02 and 5.15 +/- 0.02 respectively (solutions cont aining 30% acetonitrile in addition to DMSO to solubilise these drugs), whi ch are both stronger than chloroquine under the same conditions (log K = 4. 56 +/- 0.02). (C) 1999 Elsevier Science Inc. All rights reserved.