Departamento de Parasitologı́a, Facultad de Farmacia, Universidad de Granada, Campus de Cartuja, 18071 Granada, Spain.
Departamento de Quı́mica Farmacéutica y Orgánica, Facultad de Farmacia, Universidad de Granada, Campus de Cartuja, 18071 Granada, Spain.
J Med Chem. 2020 Jun 11;63(11):5734-5751. doi: 10.1021/acs.jmedchem.9b02016. Epub 2020 May 26.
() causes visceral, cutaneous, and mucosal leishmaniasis in humans and canine leishmaniasis in dogs. Herein, we describe that -alkyl hydroxamate derivatives displayed potent and selective activity against the amastigote stage of while no activity was observed against promastigotes. Compound showed potent activity against . Moreover, the combination of compound supported on gold nanoparticles and meglumine antimoniate was also effective and improved the activity of these compounds compared to that of the individual treatment. Docking studies showed that compound did not reach highly conserved pocket C and established interactions with the semiconserved residues V44, A45, R242, and E243 in pocket A of LiSIR2rp1. The surface space determined by these four amino acids is not conserved in human sirtuins. Compound represents a new class of selective ligands with antileishmanial activity.
() 在人类中引起内脏利什曼病、皮肤利什曼病和黏膜利什曼病,在犬中引起犬内脏利什曼病。在此,我们描述了 -烷醇羟肟酸衍生物对 的无鞭毛体阶段表现出强大而选择性的 活性,而对前鞭毛体没有活性。化合物 对 表现出强大的 活性。此外,负载在金纳米粒子上的化合物 与葡甲胺锑酸钠的组合也具有有效的 活性,并且与单独治疗相比,提高了这些化合物的活性。对接研究表明,化合物 未到达高度保守的口袋 C 并与 LiSIR2rp1 口袋 A 中的半保守残基 V44、A45、R242 和 E243 建立相互作用。这四个氨基酸确定的表面空间在人类的 sirtuins 中并不保守。化合物 代表了一类具有抗利什曼原虫活性的新型选择性配体。