Vieites Marisol, Otero Lucía, Santos Diego, Olea-Azar Claudio, Norambuena Ester, Aguirre Gabriela, Cerecetto Hugo, González Mercedes, Kemmerling Ulrike, Morello Antonio, Diego Maya Juan, Gambino Dinorah
Cátedra de Química Inorgánica, Facultad de Química, Universidad de República, Gral. Flores 2124, C. C. 1157, 11800 Montevideo, Uruguay.
J Inorg Biochem. 2009 Mar;103(3):411-8. doi: 10.1016/j.jinorgbio.2008.12.004. Epub 2008 Dec 24.
Eight new platinum(II) complexes with 3-(5-nitrofuryl)acroleine thiosemicarbazones showing anti-trypanosomal activity were synthesized, characterized and in vitro evaluated. Most of the complexes showed IC(50) values in the micromolar range against two different strains of Trypanosoma cruzi, causative agent of Chagas disease (American Trypanosomiasis). In addition, most of the newly developed complexes, together with the analogous platinum 5-nitrofuraldehyde containing thiosemicarbazones previously reported, resulted more active than the reference trypanocidal drug nifurtimox on the infective trypomastigote form of the parasite. Their capacity to produce free radicals that could lead to parasite death was evaluated by ESR experiments in the parasite and by respiration measurements. Compounds were tested for their DNA interaction ability. Results showed that some of the compounds could act as dual inhibitors in the parasite, through production of toxic free radicals and interaction with DNA. All the results were compared with those previously reported for the free ligands, the analogous palladium(II) compounds and the previously reported series of platinum(II) compounds.
合成、表征并体外评估了8种具有抗锥虫活性的含3-(5-硝基呋喃基)丙烯醛硫代半卡巴腙的新型铂(II)配合物。大多数配合物对恰加斯病（美洲锥虫病）的病原体克氏锥虫的两种不同菌株显示出微摩尔范围内的IC(50)值。此外，大多数新开发的配合物，连同先前报道的含5-硝基糠醛硫代半卡巴腙的类似铂配合物，对寄生虫的感染性锥鞭毛体形式比参比杀锥虫药硝呋替莫更具活性。通过在寄生虫中的电子自旋共振实验和呼吸测量评估了它们产生可能导致寄生虫死亡的自由基的能力。测试了化合物的DNA相互作用能力。结果表明，一些化合物可通过产生有毒自由基和与DNA相互作用，在寄生虫中充当双重抑制剂。将所有结果与先前报道的游离配体、类似钯(II)化合物和先前报道的铂(II)化合物系列的结果进行了比较。
