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-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.
Madrid
Peter B
PB
Biosciences Division, SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA. peter.madrid@sri.com
Polgar
Willma E
WE
Toll
Lawrence
L
Tanga
Mary J
MJ
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
D000995:Antitubercular Agents; D010640:Phenothiazines; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin