A series of new uncharged functional acetylcholinesterase (AChE) reactivators including heterodimers of tetrahydroacridine with 3-hydroxy-2-pyridine aldoximes and amidoximes has been synthesized. These novel molecules display in vitro reactivation potencies towards VX-, tabun- and paraoxon-inhibited human AChE that are superior to those of the mono- and bis-pyridinium aldoximes currently used against nerve agent and pesticide poisoning. Furthermore, these uncharged compounds exhibit a broader reactivity spectrum compared to currently approved remediation drugs.
Kliachyna M, Santoni G, Nussbaum V, Renou J, Sanson B, Colletier JP, Arboleas M, Loiodice M, Weik M, Jean L, Renard PY, Nachon F, Baati R (2014) Design, synthesis and biological evaluation of novel tetrahydroacridine pyridine- aldoxime and -amidoxime hybrids as efficient uncharged reactivators of nerve agent-inhibited human acetylcholinesterase Eur Journal of Medicinal Chemistry78C: 455-467
Kliachyna M, Santoni G, Nussbaum V, Renou J, Sanson B, Colletier JP, Arboleas M, Loiodice M, Weik M, Jean L, Renard PY, Nachon F, Baati R (2014) Eur Journal of Medicinal Chemistry78C: 455-467