Organoarsenicals derived from 2-phenyl-[1,3,2dithiarsolan-4-yl)-methanol (AsIII) with antileukaemic properties: from trypanosomicides to anticancer drugs

• Published in: Annales pharmaceutiques françaises Vol. 65; no. 3; p. 162
• Main Authors: Gibaud, S, Astier, A
• Format: Journal Article
• Language: French
• Published: France 01.05.2007
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Arsenicals - chemical synthesis; Arsenicals - pharmacology; Arsenicals - therapeutic use; Humans; Leukemia - drug therapy; Trypanocidal Agents - chemical synthesis; Trypanocidal Agents - pharmacology; Trypanocidal Agents - therapeutic use
• ISSN: 0003-4509

For several decades, organometallic and organometalloid compounds have played an important part in anticancer chemotherapies, in particular those derived from platinum. Trivalent arsenic, in the form of arsenic trioxide (As2O3; Trisenox(R)) is currently used in the treatment of refractory leukemias, but at the cost of major adverse effects. Moreover, recent studies showed that the trypanocide melarsoprol, could be more effective than arsenic trioxide on myelogenous leukaemias. We have synthesized a series of derivatives from 2-phenyl-[1,3,2]dithiarsolan-4-yl)-methanol (AsIII). Our work shows that the substitution of the aromatic ring by an iodine atom in the ortho position or by an amino-dimethoxytriazin group in the para position increases very significantly the antileukemic activity and improves the therapeutic index (IT=LD50/IC50) of these melarsoprol-derivatives molecules, as compared to arsenic trioxide. However, one of the most promising compounds seems to be arsthinol, an old drug used in the past as an amebicide. Nanoparticle carriers of melarsoprol were also prepared for the purpose of modifying its tissue distribution reduce its brain toxicity.