Fig 1.
R-oxamniquine and S-oxamniquine indicating the functional groups and the chiral carbons (red circles).
The absolute configurations are determined by the substituents coming off of the chiral carbon atom using the Cahn-Ingold-Prelog rules. The molecules are rotated such that the lowest priority substituent (H-atom) is in the back of the chiral carbon, facing away from the viewer. Curves are drawn from substituents 1 to 2 to 3 substituent. If two substituents have the same immediate substituent atom, evaluate atoms progressively further away from the chiral center until a difference is found. If the curve is clockwise, the stereocenter is of R-configuration. If the curve is counterclockwise, the stereocenter is of S-confguration.
Fig 2.
A) Separation of oxamniquine stereoisomers by HPLC on a chiral column. B) HPLC purity control on the same column of a pool of fractions # 1 obtained from several runs like the one depicted in A. C) HPLC purity control on the same column of a pool of fractions # 2 obtained from several runs like the one depicted in A.
Fig 3.
Separation of oxamniquine stereoisomers by capillary zone electrophoresis.
Top: profile of racemic oxamniquine alone. Bottom: profile of racemic oxamniquine spiked with isomer #1 (arrow) purified by HPLC.
Fig 4.
Oxamniquine enantiomers bound to the SmSULT active site.
A) 1.8 Å electron density calculated with coefficients 2mFo-DFc contoured at 1.0σ superimposed on the refined structure of the R-OXA•SmSULT•PAP complex. Numbers represent H-bond lengths in Å. B) 1.3 Å electron density calculated with coefficients 2mFo-DFc contoured at 1.0σ superimposed on the structure of the S-OXA•SmSULT•PAP complex. Note: some structural elements have been removed for clarity.
Table 1.
X-ray diffraction data collection and refinement statistics.
Fig 5.
A) Superimposed structures of R- and S-OXA complex structures in yellow and green, respectively. Hydrogen bonding distances are indicated as dashed lines with distances in Å. B) Alternate view of superimposed enantiomer complex structures highlighting the pucker of the piperidine ring. The chiral carbon is marked (*). Note: some structural elements have been removed for clarity.
Table 2.
Effects of OXA and its separate enantiomers on S. mansoni kept in vitro.
Morphological appeareance and movements of worms were recorded two or three weeks after drug exposure, for high and low doses respectively.