一种用于治疗片形吸虫病的高度水溶性苯并咪唑衍生物。
A highly water soluble benzimidazole derivative useful for the treatment of fasciolosis.
作者信息
Flores-Ramos Miguel, Ibarra-Velarde Froylán, Hernández-Campos Alicia, Vera-Montenegro Yolanda, Jung-Cook Helgi, Cantó-Alarcón Germinal J, Del Rivero Lauro Misael, Castillo Rafael
机构信息
Facultad de Química, Departamento de Farmacia, UNAM, México DF 04510, Mexico.
Facultad de Medicina Veterinaria y Zootecnia, Departamento de Parasitología, UNAM, México, DF 04510, Mexico.
出版信息
Bioorg Med Chem Lett. 2014 Dec 15;24(24):5814-5817. doi: 10.1016/j.bmcl.2014.10.017. Epub 2014 Oct 13.
This study describes the synthesis of compound (7), a highly hydrosoluble phosphonooxymethyl prodrug of compound alpha (4). Compound (7) improved the aqueous solubility of its precursor compound (4) by 50,000 times and it is stable at neutral pH. The prodrug showed faciolicidal activity when evaluated in vitro against excysted Fasciola hepatica metacercariae. The in vivo evaluation of (7) was carried out via oral, intramuscular and subcutaneous administration in sheep artificially infected with F. hepatica metacercariae. At an intramuscular dose of 4 mg/kg, the activity of (7) was similar to that of compound alpha (4) at an oral dose of 15 mg/kg.
本研究描述了化合物（7）的合成，它是化合物α（4）的一种高度水溶性的膦酰氧基甲基前药。化合物（7）将其前体化合物（4）的水溶性提高了50000倍，并且在中性pH条件下稳定。在前体药物针对脱囊的肝片形吸虫尾蚴进行体外评估时，显示出杀片形吸虫活性。通过对人工感染肝片形吸虫尾蚴的绵羊进行口服、肌肉注射和皮下注射，对（7）进行了体内评估。在肌肉注射剂量为4mg/kg时，（7）的活性与口服剂量为15mg/kg时化合物α（4）的活性相似。
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