Davis Jonathan, Cetto Anne, Campbell Mary, Scoggins Seth, Stultz Laura, Hanson Pamela
Department of Biology, Furman University, Greenville, SC 29613, USA.
Department of Chemistry, Birmingham-Southern College, Birmingham, AL 35254, USA.
MicroPubl Biol. 2021 Aug 4;2021. doi: 10.17912/micropub.biology.000436. eCollection 2021.
Low solubility in aqueous solutions is a significant limitation of the otherwise promising anticancer ruthenium complex KP1019. In laboratory studies, this challenge is often overcome by using DMSO to help drive the drug into solution. Since DMSO was previously shown to alter the bioactivity of platinum-based chemotherapeutics, here we examine DMSO's effects on KP1019. Using as a model organism, we apply multiple measures of growth inhibition to demonstrate that DMSO reduces the drug's toxicity. This reduction in bioactivity correlates with spectrophotometric changes consistent with DMSO-dependent increases in the stability of the KP1019 pro-drug. The impact of DMSO on the biology and chemistry of KP1019 suggests this solvent should not be used in studies of this and similar anticancer ruthenium complexes.
在水溶液中溶解度低是颇具前景的抗癌钌配合物KP1019的一个重大局限。在实验室研究中,这一难题通常通过使用二甲基亚砜(DMSO)来帮助药物溶解得以克服。由于之前已表明DMSO会改变铂类化疗药物的生物活性,因此我们在此研究DMSO对KP1019的影响。以[具体生物名称未给出]作为模式生物,我们应用多种生长抑制指标来证明DMSO会降低该药物的毒性。这种生物活性的降低与分光光度法变化相关,这些变化与DMSO依赖的KP1019前药稳定性增加一致。DMSO对KP1019生物学和化学性质的影响表明,在对该及类似抗癌钌配合物的研究中不应使用这种溶剂。