2,3-Dithioerythritol, a possible new arsenic antidote

Area of Science:

• Toxicology
• Medicinal Chemistry
• Pharmacology

Background:

• British antilewisite (2,3-dimercaptopropanol; BAL) is a traditional arsenic antidote but has significant toxicity.
• Organic arsenic compounds pose a toxicological challenge requiring effective antidotes.
• Existing antidotes like BAL have limitations in therapeutic efficacy and safety.

Purpose of the Study:

• To synthesize and evaluate novel, less toxic derivatives of BAL as potential antidotes for organic arsenic poisoning.
• To compare the efficacy and cytotoxicity of these new BAL derivatives against BAL and DMSA.
• To assess the ability of the compounds to protect cells from phenyldichloroarsine (PDA) toxicity.

Main Methods:

• Synthesis of two BAL derivatives: 2,3-dithioerythritol (DTE) and a dithiolane.
• Reaction of synthesized compounds with phenyldichloroarsine (PDA) to form cyclic dithioarsolanes.
• Assessment of cytotoxicity and cell survival rescue in PDA-poisoned mouse lymphoma cells in culture.

Main Results:

• Both DTE and the dithiolane derivative reacted with PDA to form the expected cyclic dithioarsolanes.
• The dithiolane derivative showed poor performance as an antidote in the cell culture system.
• DTE exhibited lower cytotoxicity than BAL and DMSA, and significantly improved cell survival in PDA-exposed cells.

Conclusions:

• 2,3-dithioerythritol (DTE) is a promising less toxic alternative to BAL for treating organic arsenic poisoning.
• DTE's superior efficacy in protecting cells from PDA toxicity highlights its potential therapeutic value.
• Further investigation into DTE as an arsenic antidote is warranted based on its improved safety and efficacy profile.