RESUMO
"Novichoks" is the name given to the controversial chemical weapons supposedly developed in the former Soviet Union between the 1970s and the 1990s. Designed to be undetectable and untreatable, these chemicals became the most toxic of the nerve agents, being very attractive for both terrorist and chemical warfare purposes. However, very little information is available in the literature, and the Russian government did not acknowledge their development. The intent of this review is to provide the IJMS readers with a general overview on what is known about novichoks today. We briefly tell the story of the secret development of these agents, and discuss their synthesis, toxicity, physical-chemical properties, and possible ways of treatment and neutralization. In addition, we also wish to call the attention of the scientific community to the great risks still represented by nerve agents worldwide, and the need to keep constant investments in the development of antidotes and ways to protect against such deadly compounds.
Assuntos
Substâncias para a Guerra Química/química , Substâncias para a Guerra Química/toxicidade , Guerra Química , Agentes Neurotóxicos/química , Agentes Neurotóxicos/toxicidade , Organofosfatos/química , Organofosfatos/toxicidade , Animais , Fenômenos Químicos , Guerra Química/prevenção & controle , Substâncias para a Guerra Química/síntese química , Descontaminação , Humanos , Agentes Neurotóxicos/síntese química , Organofosfatos/síntese químicaRESUMO
In this work we present the synthesis, aqueous solubility and stability, hydrolysis by alkaline phosphatase, and in vivo fasciolicidal activity in sheep of a highly water soluble phosphate salt prodrug of triclabendazole (MFR-5). The aqueous solubility of MFR-5 at pH 7 was 88,000-fold that of triclabendazole. MFR-5 showed excellent aqueous stability (>95% after 26h) at pH 7, making it ideal for developing pharmaceutical compositions in the form of solutions that can easily be hydrolyzed by the enzyme alkaline phosphatase (t=13.6s) to liberate the precursor compound. An aqueous solution of MFR-5 administered intramuscularly to sheep at concentrations of 4, 6 and 8mg/kg presented a fasciolicidal efficiency of 96.5%, 98.4% and 99.2%, respectively. In the in vivo experiments, MFR-5 reduced 100% the excretion of eggs in all of the above concentrations.