title: Structural requirements for the antitubercular quaternized triflupromazine pharmacophore.
abstract: Quaternized triflupromazine derivatives (QTDs) must possess benzyl groups attached to the quaternary nitrogen in order to have significant antitubercular potency. Replacing the quaternary amine with a triazole abolishes antitubercular activity. A modest halogen substitution effect exists, with the 4-bromophenyl QTD 3 having the best selectivity index (>21). All N-benzyl QTDs 1-4 similarly inhibit non-replicating, persistent Mycobacterium tuberculosis with MIC<8 μM, and compounds 1-3 were all nontoxic to mammalian cells in vitro (IC(50)>128 μM).
authors: Department of Chemistry, Salisbury University, Salisbury, MD 21801, USA.
authors: Dominique L
authors: DL
authors: Kunciw
authors: Jacob J
authors: JJ
authors: Liechty
authors: Miguel O
authors: MO
authors: Mitchell
authors: Baojie
authors: B
authors: Wan
authors: Scott G
authors: SG
authors: Franzblau
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014273:Triflupromazine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014376:Tuberculosis / Q000188:drug therapy; D014709:Vero Cells
chemical_list: D000995:Antitubercular Agents; D014273:Triflupromazine