title: Synthesis and antitubercular activity of phenothiazines with reduced binding to dopamine and serotonin receptors.
abstract: 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-HT(1A), 5-HT(2A), and 5-HT(2C). The most active compounds showed MICs from 2 to 4 microg/mL and had overall reduced binding to the dopamine and serotonin receptors compared to chlorpromazine and trifluoperazine.
authors.affiliation: Biosciences Division, SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA. peter.madrid@sri.com
authors.forename: Peter B
authors.initials: PB
authors.lastname: Madrid
authors.forename: Willma E
authors.initials: WE
authors.lastname: Polgar
authors.forename: Lawrence
authors.initials: L
authors.lastname: Toll
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Tanga
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D010640:Phenothiazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011954:Receptors, Dopamine / Q000737:chemistry; D011985:Receptors, Serotonin / Q000737:chemistry
chemical_list: D000995:Antitubercular Agents; D010640:Phenothiazines; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin