BioCentury
ARTICLE | Distillery Therapeutics

Therapeutics: An undetermined target

September 17, 2015 7:00 AM UTC

In vitro studies identified thioridazine analogs that could help treat tuberculosis. Chemical synthesis of thioridazine analogs lacking the phenothiazine structure associated with thioridazine's neuroleptic side effects, followed by testing in bacterial efflux assays, yielded four compounds that inhibited efflux activity in Mycobacterium tuberculosis by 33-122% compared with thioridazine, and were less cytotoxic in human monocyte-derived macrophages than thioridazine. In M. tuberculosis cultures, each of the four compounds plus first- or second-line tuberculosis drugs decreased bacterial growth synergistically compared with the drugs alone. Next steps include testing one of the lead compounds in mouse models of tuberculosis...