Thioridazine: resurrection as an antimicrobial agent?

Area of Science:

• Pharmacology
• Microbiology
• Medicinal Chemistry

Background:

• Multidrug-resistant bacterial strains necessitate new antimicrobial therapies.
• Thioridazine, an antipsychotic, possesses antimicrobial properties but has dose-limiting side effects.
• Cardiotoxicity of thioridazine is structurally specific, while antimicrobial activity is shared by analogues.

Purpose of the Study:

• To explore the potential of thioridazine enantiomers and its metabolite as novel antimicrobial drug leads.
• To address the need for affordable antimicrobial agents against infectious diseases.

Main Methods:

• Investigated the structure-activity relationship of thioridazine and its analogues.
• Examined the potential of thioridazine's enantiomers and ring sulphoxide metabolite.

Main Results:

• Antimicrobial properties of thioridazine are distinct from its cardiotoxicity.
• Phenothiazine analogues share antimicrobial activity, suggesting a separable mechanism.
• Thioridazine's enantiomers or its ring sulphoxide metabolite show promise.

Conclusions:

• Thioridazine's enantiomers or its ring sulphoxide metabolite could serve as future antimicrobial drug leads.
• Separating antimicrobial activity from cardiotoxicity is feasible for drug development.
• This research offers a potential strategy to combat infectious diseases.