Mota Vinicius Zamprogno, de Carvalho Gustavo Senra Gonçalves, da Silva Adilson David, Costa Luiz Antônio Sodré, de Almeida Machado Patrícia, Coimbra Elaine Soares, Ferreira Carmen Veríssima, Shishido Silvia Mika, Cuin Alexandre
LQBin, Laboratório de Química BioInorgânica, Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, 36036-330, Brazil.
Biometals. 2014 Feb;27(1):183-94. doi: 10.1007/s10534-014-9703-1. Epub 2014 Jan 19.
Synthesis, characterization, DFT studies and biological assays of new gold(I) and gold(III) complexes of benzimidazole are reported. Molecular and structural characterizations of the compounds were based on elemental (C, H and N) and thermal (TG-DTA) analyses, and FT-IR and UV-Visible spectroscopic measurements. The structures of complexes were proposed based DFT calculations. The benzimidazole compounds (Lig1 and Lig2) and the gold complexes were tested against three Leishmania species related to cutaneous manifestations of leishmaniasis. The free benzimidazole compounds showed no leishmanicidal activity. On the other hand, the gold(I and III) complexes have shown to possess significant activity against Leishmania in both stages of parasite, and the gold(III) complex with Lig2 exhibited expressive leishmanicidal activity with IC50 values below 5.7 μM. Also, the gold complexes showed high leishmania selectivity. The gold(I) complex with Lig1, for example, is almost 50 times more toxic for the parasite than for macrophages. Besides the leishmanicidal activity, all complexes exhibited toxic effect against SK-Mel 103 and Balb/c 3T3, cancer cells.
报道了新型苯并咪唑金(I)和金(III)配合物的合成、表征、密度泛函理论(DFT)研究及生物学测定。化合物的分子和结构表征基于元素分析(碳、氢和氮)、热分析(热重-差热分析)以及傅里叶变换红外光谱(FT-IR)和紫外可见光谱测量。基于DFT计算提出了配合物的结构。对苯并咪唑化合物(配体1和配体2)以及金配合物针对三种与利什曼病皮肤表现相关的利什曼原虫物种进行了测试。游离苯并咪唑化合物未显示出杀利什曼原虫活性。另一方面,金(I)和金(III)配合物在寄生虫的两个阶段均显示出对利什曼原虫具有显著活性,并且与配体2形成的金(III)配合物表现出明显的杀利什曼原虫活性,半数抑制浓度(IC50)值低于5.7 μM。此外,金配合物显示出高的利什曼原虫选择性。例如,与配体1形成的金(I)配合物对寄生虫的毒性比对巨噬细胞的毒性几乎高50倍。除了杀利什曼原虫活性外,所有配合物对SK-Mel 103和Balb/c 3T3癌细胞均表现出毒性作用。