Carbohydrate-conjugated 4-(1,3,2-dithiarsolan-2-yl)aniline as a cytotoxic agent against colorectal cancer.

Arsenic trioxide (AsO) has been approved for the treatment of acute promyelocytic leukemia (APL); however, its use in the treatment of solid tumors is limited due to its pharmacokinetic properties. Organic arsenic compounds provide better options for pharmaceutical optimization. -Aminophenyl arsenoxide (-APAO), an organic arsenic compound, was found to interact with the promyelocytic leukemia-retinoic acid receptor alpha (PML-RARα) fusion protein in a similar manner to arsenic trioxide. Analogs of -APAO such as 4-(1,3,2-dithiarsolan-2-yl)aniline (-APDTAs) were recently found to show improved cytotoxicity toward several solid tumor cell lines with lower toxicity to normal cells. Here, we synthesized a carbohydrate-conjugated 4-(1,3,2-dithiarsolan-2-yl)aniline (-APDTAs) and showed that it exhibited reduced cytotoxicity to normal cells, suggesting a feasible approach to improve the therapeutic index of arsenic-containing compounds as chemotherapeutic agents.