title: 2,3-Dithioerythritol, a possible new arsenic antidote.
abstract: British antilewisite (2,3-dimercaptopropanol; BAL) has long been used as an arsenic antidote, but its therapeutic efficacy is limited by its inherent toxicity. We synthesized two less toxic derivatives of BAL and investigated their potential as antidotes to organic arsenic. The new compounds, 2,3-dithioerythritol (DTE) and 2,2-dimethyl-4-(hydroxymethyl)-1,3-dithiolane (isopropylidene derivative of BAL), react readily with phenyldichloroarsine (PDA) to yield the expected corresponding cyclic 1,3-dithioarsolanes. The BAL derivatives were compared to BAL in terms of their cytotoxicity and their ability to rescue PDA-poisoned mouse lymphoma cells in culture. The dithiolane was not a good antidote in the cultured cell system. In contrast, DTE was less toxic than BAL or DMSA and was superior at improving cell survival in PDA-exposed cells.
authors.affiliation: Division of Biophysical Research, Letterman Army Institute of Research, Presidio of San Francisco, California 94129-6800.
authors.forename: V L
authors.initials: VL
authors.lastname: Boyd
authors.forename: J W
authors.initials: JW
authors.lastname: Harbell
authors.forename: R J
authors.initials: RJ
authors.lastname: O'Connor
authors.forename: E L
authors.initials: EL
authors.lastname: McGown
mesh_terms: D000818:Animals; D000931:Antidotes; D020261:Arsenic Poisoning; D001152:Arsenicals / Q000737:chemistry; D004112:Dimercaprol / Q000494:pharmacology / Q000633:toxicity; D004226:Dithioerythritol / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D008223:Lymphoma / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D004113:Succimer / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000931:Antidotes; D001152:Arsenicals; D004112:Dimercaprol; D004226:Dithioerythritol; C053663:phenyldichloroarsine; D004113:Succimer