ABSTRACT
Hydroxychloroquine (HCQ) was noted to produce severe cardiac arrhythmia, an adverse effect as its use against severe acute respiratory syndrome caused by coronavirus 2 (SAES-CoV-2). HCQ is an antimalarial drug with quinoline structure. Some other quinoline compounds, such as fluoroquinolone antibiotics (FQs), also lead to arrhythmias characterized by QT prolongation. QT prolongation is usually related to the human ether-a-go-go-related gene (hERG) potassium channel inhibitory activity of most drugs. In this research, molecular docking was used to study the potential inhibitory activities of HCQ as well as other quinolines derivatives and hERG potassium channel protein. The possible causes of these QT prolongation effects were revealed. Molecular docking and patch clamp experiments showed that HCQ could bind to hERG and inhibit the efflux of potassium ion preferentially in the repolarization stage. The IC50 of HCQ was 8.6 µM ± 0.8 µM. FQs, which are quinoline derivatives, could also bind to hERG molecules. The binding energies of FQs varied according to their molecular polarity. It was found that drugs with a quinoline structure, particularly with high molecular polarity, can exert a significant potential hERG inhibitory activity. The potential side effects of QT prolongation during the development and use of quinolines should be carefully considered.