Arsenical-based cancer drugs

Arsenic is a semi-metal or metalloid with two biologically important oxidation states, As(III) and As(V). As(III), in particular, reacts with closely spaced protein thiols, forming stable cyclic dithioarsinite complexes in which both sulfur atoms are bound to arsenic. It is this reaction that is mostly responsible for arsenics cytotoxicity. Arsenic compounds have been used as medicinal agents for many centuries for the treatment of diseases such as psoriasis, syphilis, and rheumatosis. From the 1700’s until the introduction of and use of modern chemotherapy and radiation therapy in the mid 1900’s, arsenic was a mainstay in the treatment of leukemia. Concerns about the toxicity of arsenical compounds led eventually to their abandonment for the treatment of cancer. The discovery in the 1980’s that arsenic trioxide induces complete remission in a high percentage of patients with acute promyelocytic leukemia has awakened interest in this metalloid for the treatment of human disease. In particular, a new class or organoarsenicals are being trialed for the treatment of hematological malignancies and solid tumors. In this review, we discuss the arsenical-based compounds used in the past and present for the treatment of various forms of cancer. Mechanisms of action and selectivity and acute and chronic toxicities are discussed along with the prospects of this class of molecule.