(2-Phenyl-[1,3,2]dithiarsolan-4-yl)-methanol derivatives show in vitro antileukemic activity

Pharmacokinetics and tissue distribution of the antileukaemic organoarsenicals arsthinol and melarsoprol in mice

“…This fact is of a crucial importance to explain the excellent activity of As III organic derivatives against leukaemia cells located into the bone marrow. However, the lower ability of arsthinol than melarsoprol to accumulate into bone marrow could be compensated by its higher antileukaemic activity, as we demonstrated on two human cancer cells lines [6]. Actually, the total arsenic level into bone marrow does not entirely reflect the antileukaemic activity of the organoarsenicals.…”

“…Moreover, melarsoprol has been shown to be very effective on various leukaemia cell lines but its human use has been hampered by severe encephalopathy [4,5]. Recently, we synthesized new derivatives of (2-phenyl- [1,3,2]dithiarsolan-4-yl)-methanol which exhibited an increased cytotoxic activity on U937 and K562 human cell lines, as compared to As 2 O 3 and melarsoprol [6]. The tissue distribution of these compounds remains a key point since the bone marrow is considered as the site of action and the central nervous system (CNS) as the site of the main toxicity.…”

“…1b), also known as Balarsen Ò , was first time synthesized more than 50 years ago [7], and it has been shown to have amoebicidal [8] and bactericidal [9,10] activities. Moreover, we have previously demonstrated that this drug exhibited also an antileukaemic activity with a best therapeutic index than arsenic trioxide and melarsoprol, as estimated by the ratio LD 50 /IC 50 [6]. Thus, this promising compound was chosen for further experiments and this work has compared the blood kinetics and the tissue distribution of melarsoprol and arsthinol in the liver, bone marrow and brain, after IV injection to mouse.…”

Speciation of arsenic in urine following intravenous administration of arsthinol in mice

“…The synthesis of arsthinol was performed following the method previously described (Gibaud et al 2006). Acetarsol ( Fig.…”

“…Based on these results, studies have been carried out on trivalent organoarsenic dithiarsolanes (Gibaud et al 2006;Ben Zirar et al 2007). These investigations have shown that arsthinol (Fig.…”