title: The complex role of the triphenylmethyl motif in anticancer compounds.
abstract: Compounds incorporating the triphenylmethyl motif constitute an emerging family of potent anticancer agents. Although several small molecules containing this pharmacophore have now been identified, the mechanism of cell death induction for some of these compounds is unknown. In an effort to define their mechanism of action, and to distinguish subtypes within the group of compounds containing the triphenylmethyl moiety, we have created novel triphenylmethyl-containing small molecules and have evaluated them in a battery of biological assays. Here we show that several phosphonate and phosphonochloridates possessing the triphenylmethyl motif potently induce death of multiple cancer cell lines in culture. Further assays evaluating the ability to cause cell cycle arrest, inhibit tubulin polymerization, dissociate mitochondrial-bound hexokinase in cancer cells, and inhibit calcium-dependent potassium ion channels indicate that triphenylmethyl-containing compounds can be placed into at least four distinct categories, each with a different mechanism of action.
authors.affiliation: Department of Chemistry, Roger Adams Laboratory, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Palchaudhuri
authors.forename: Vitaliy
authors.initials: V
authors.lastname: Nesterenko
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hergenrother
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D006593:Hexokinase / Q000037:antagonists & inhibitors; D006801:Humans; D063065:Organophosphonates; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D014320:Triphenylmethyl Compounds / Q000737:chemistry / Q000494:pharmacology*; D014404:Tubulin / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D063065:Organophosphonates; D024681:Potassium Channels, Calcium-Activated; D014320:Triphenylmethyl Compounds; D014404:Tubulin; D006593:Hexokinase