Multi-resistant bacteria may be re-sensitized towards antibiotic drugs by a group of compounds termed Phenothiazines1. The mechanism of re-sensitization is uncertain, however, the wide range of effects caused by phenothiazines suggests that the unspecific physical interaction with a biomembrane may play a significant role. Chemically, thioridazine is small (370.57 g/mol) and chiral. Clinically, the molecule is an antipsychotic agent, and in therapy, usually the racemate is administered. The drug is known to be cardiotoxic at high concentration. However, the antibiotic impact was reported to appear at very low amounts. Preliminary results hint towards a variation in the enantiomer activity, especially a stereoselective tissue uptake that affects antipsychotic activity as well as cardiotoxicity2,3. This presentation will outline a project that focuses on the physical associations of thioridazine enantiomers with biomembrane models. Lipid vesicles will be formulated from well-established protocols with conventional lipid compositions, and attempts will then be made to approach bacterial membrane liposome models. The main method of choice is isothermal titration calorimetry, which will be employed to discern variances in binding constants between thioridazine enantiomers as well as the racemic mixture.
|Publication status||Published - 2014|