Caballero Ana B, Rodríguez-Diéguez Antonio, Salas Juan M, Sánchez-Moreno Manuel, Marín Clotilde, Ramírez-Macías Inmaculada, Santamaría-Díaz Noelia, Gutiérrez-Sánchez Ramón
Departamento de Química Inorgánica, Universidad de Granada, Severo Ochoa s/n, 18071 Granada, Spain.
Departamento de Química Inorgánica, Universidad de Granada, Severo Ochoa s/n, 18071 Granada, Spain.
J Inorg Biochem. 2014 Sep;138:39-46. doi: 10.1016/j.jinorgbio.2014.04.016. Epub 2014 May 6.
In the last years, numerous and significant advances in lanthanide coordination chemistry have been achieved. The unique chemical nature of these metal ions which is conferred by their f-electrons has led to a wide range of coordination compounds with interesting structural, physical and also biological properties. Consequently, lanthanide complexes have found applications mainly in catalysis, gas adsorption, photochemistry and as diagnostic tools. However, research on their therapeutic potential and the understanding of their mechanism of action is still taking its first steps, and there is a distinct lack of research in the parasitology field. In the present work, we describe the synthesis and physical properties of seven new lanthanide complexes with the anionic form of the bioactive ligand 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one (HmtpO), namely [Ln(mtpO)3(H2O)6]·9H2O (Ln=La(III), Nd(III), Eu(III), Gd(III), Tb(III), Dy(III) and Er(III)). In addition, results on the in vitro antiproliferative activity against Leishmania spp. and Trypanosoma cruzi are described. The high activity of the new compounds against parasite proliferation and their low cytotoxicity against reference host cell lines show a great potential of this type of compounds to become a new generation of highly effective and non-toxic antiparasitic agents to fight the so considered neglected diseases leishmaniasis and Chagas disease.
在过去几年中，镧系元素配位化学取得了众多重大进展。这些金属离子独特的化学性质由其f电子赋予，导致了大量具有有趣结构、物理和生物学性质的配位化合物。因此，镧系元素配合物主要在催化、气体吸附、光化学以及作为诊断工具等方面得到了应用。然而，关于它们的治疗潜力及其作用机制的研究仍处于起步阶段，并且在寄生虫学领域明显缺乏相关研究。在本工作中，我们描述了七种新型镧系元素配合物的合成及其物理性质，这些配合物与生物活性配体5-甲基-1,2,4-三唑并[1,5-a]嘧啶-7(4H)-酮（HmtpO）的阴离子形式配位，即[Ln(mtpO)3(H2O)6]·9H2O（Ln = La(III)、Nd(III)、Eu(III)、Gd(III)、Tb(III)、Dy(III)和Er(III)）。此外，还描述了这些化合物对利什曼原虫属和克氏锥虫的体外抗增殖活性结果。新化合物对寄生虫增殖具有高活性，且对参考宿主细胞系具有低细胞毒性，这表明这类化合物具有成为新一代高效无毒抗寄生虫药物以对抗被视为被忽视疾病的利什曼病和恰加斯病的巨大潜力。
