Comparison of Antibacterial Activity of (-) Thioridazine and Racemic Thioridazine in Staphylococcus aureus

Antibiotic resistance is an increasing problem globally. Non-antibiotics are therapeutics that have antibacterial properties in addition to their original purposes. Thioridazine is a non-antibiotic that has been shown to sensitize Staphylococcus aureus to classical antibiotics. However, the drug has been withdrawn from the market due to cardiotoxicity. Recent work has shown that the cardiotoxic side-effects are linked to the (+) enantiomer of thioridazine but not to the (-) form. The aim of this work was thus to investigate the antimicrobial efficacy of the (-) enantiomer (-TZ) as compared to the racemic mixture of Thioridazine (TZR). Viability assays on methicillin-sensitive and methicillin-resistant Staphylococcus aureus (S. aureus) strains show that combinations of TZR and-TZ together with Dicloxacillin (DCX) are equally effective showing that selecting the -TZ enantiomer does not compromise its activity. Importantly, -TZ binds with lower affinity to the dopamine 2 receptor, indicating that this formulation might provide therapeutic benefit with reduced side effects. This strengthens the potential for future application of combined treatment using -TZ and classical antibiotics.