ABSTRACT
Quinine, a quinoline derivative, is an ancient antipyretic drug with antimalarial properties that has been phased out by more effective synthetic candidates. In previous studies we discovered that hydroxychloroquine (HCQ), a synthetic antimalarial with structural similarities to quinine, reduced the binding of antiphospholipid (aPL) immune complexes to phospholipid bilayers. We performed ellipsometry and atomic force microscopy (AFM) studies to measure the effect of quinine on dissociation of anti-ß2-glycoprotein I (anti-ß2GPI) immune complexes. We found that quinine desorbed pre-formed ß2GPI-aPL immunoglobulin (Ig)G complexes from phospholipid bilayers at significantly lower molar concentrations than HCQ. Quinine also inhibited the formation of immune complexes with a higher efficacy than HCQ at equivalent drug concentrations of 0.2 mg/ml (0.192 ± 0.025 µg/cm(2) for quinine vs. 0.352 ± 0.014 µg/cm(2) for HCQ, p < 0.001). Furthermore, AFM imaging experiments revealed that addition of quinine disintegrated immune complexes bound to planar phospholipid layers. The desorptive and inhibitory effects of the old drug, quinine, toward ß2GPI-aPL IgG complexes and ß2GPI were significantly more pronounced compared to the synthetic antimalarial, HCQ. The results suggest that the quinoline core of the molecule is a critical domain for this activity and that side chains may further modulate this effect. The results also indicate that there may yet be room for considering new activities of very old drugs in devising clinical trials on potential non-anticoagulant treatments for antiphospholipid syndrome (APS).
