Synthesis and antitubercular activity of phenothiazines with reduced binding to dopamine and serotonin receptors

Analogs of the psychotropic phenothiazines were synthesized and examined as antitubercular agents against Mycobacterium tuberculosis H37Rv. The compounds were subsequently counter-screened for binding to the dopaminergic-receptor subtypes D1, D2, D3 and the serotonergic-receptor subtypes 5-HT1A, 5-HT2A, and 5-HT2C. The most active compounds showed MICs from 2 to 4 μg/mL and had overall reduced binding to the dopamine and serotonin receptors compared to chlorpromazine and trifluoperazine.

Graphical abstractA series of phenothiazines were synthesized and evaluated for activity against Mycobacterium tuberculosis. The compounds were subsequently counter-screened for binding to dopamine and serotonin receptors to determine the in vitro selectivity of the compounds for antitubercular activity over psychotropic effects.Figure optionsDownload full-size imageDownload as PowerPoint slide