Freijo Mónica Blanco, López-Arencibia Atteneri, Piñero José E, McNaughton-Smith Grant, Abad-Grillo Teresa
Instituto Universitario de Bio-Orgánica 'Antonio González', Departamento de Química Orgánica, Universidad de La Laguna, Avda. Fco. Sánchez 2, 38206 La Laguna, Tenerife, Spain.
Instituto Universitario de Enfermedades Tropicales y Salud Pública de Las Islas Canarias, Laboratorio de Quimioterapias de Protozoos, Universidad de La Laguna, Tenerife, Spain.
Eur J Med Chem. 2018 Jan 1;143:1312-1324. doi: 10.1016/j.ejmech.2017.10.032. Epub 2017 Oct 14.
Screening of a designed collection of mono-substituted amino-1H-phenalen-1-ones against promastigote forms of L. donovani and L. amazonensis, identified seven compounds with anti-leishmanial activities comparable or better than the commonly prescribed anti-leishmanial drug, miltefosine. Structure-activity analysis revealed that appendages containing a basic tertiary nitrogen were favored, and that the position of the appendage also affected their potency. Like miltefosine, several of these active compounds significantly reduced the mitochondrial membrane potential in promastigotes. Further studies in amastigotes of L. amazonensis revealed that compounds 14, 15 and 33 were more active and more selective than miltefosine, with sub-micromolar potencies and selectivity indices >100.
对一组设计的单取代氨基-1H-菲-1-酮针对杜氏利什曼原虫和亚马逊利什曼原虫前鞭毛体形式进行筛选，鉴定出七种具有抗利什曼活性的化合物，其活性与常用的抗利什曼药物米替福新相当或更好。构效分析表明，含有碱性叔氮的取代基是有利的，并且取代基的位置也影响其效力。与米替福新一样，这些活性化合物中的几种显著降低了前鞭毛体中的线粒体膜电位。对亚马逊利什曼原虫无鞭毛体的进一步研究表明，化合物14、15和33比米替福新更具活性和选择性，具有亚微摩尔效力和大于100的选择性指数。
