Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA.
Department of Chemistry, Portland State University, Portland, OR 97207, USA.
Molecules. 2020 Jul 17;25(14):3272. doi: 10.3390/molecules25143272.
Rhodamine derivatives have been widely investigated for their mitochondrial targeting and chemotherapeutic properties that result from their lipophilic cationic structures. In previous research, we have found that conversion of Rhodamine 6G into nanoGUMBOS, i.e., nanomaterials derived from a group of uniform materials based on organic salts (GUMBOS), led to selective chemotherapeutic toxicity for cancer cells over normal cells. Herein, we investigate the chemotherapeutic activity of GUMBOS derived from four different rhodamine derivatives, two bearing an ester group, i.e., Rhodamine 123 (R123) and SNAFR-5, and two bearing a carboxylic acid group, i.e., rhodamine 110 (R110) and rhodamine B (RB). In this study, we evaluate (1) relative hydrophobicity via octanol-water partition coefficients, (2) cytotoxicity, and (3) cellular uptake in order to evaluate possible structure-activity relationships between these different compounds. Intriguingly, we found that while GUMBOS derived from R123 and SNAFR-5 formed nanoGUMBOS in aqueous medium, no distinct nanoparticles are observed for RB and R110 GUMBOS. Further investigation revealed that the relatively high water solubility of R110 and RB GUMBOS hinders nanoparticle formation. Subsequently, while R123 and SNAFR-5 displayed selective chemotherapeutic toxicity similar to that of previously investigated R6G nanoGUMBOS, the R110 and RB GUMBOS were lacking in this property. Additionally, the chemotherapeutic toxicities of R123 and SNAFR-5 nanoGUMBOS were also significantly greater than R110 and RB GUMBOS. Observed results were consistent with decreased cellular uptake of R110 and RB as compared to R123 and SNAFR-5 compounds. Moreover, these results are also consistent with previous observations that suggest that nanoparticle formation is critical to the observed selective chemotherapeutic properties as well as the chemotherapeutic efficacy of rhodamine nanoGUMBOS.
香豆素衍生物因其具有亲脂性阳离子结构而被广泛研究用于靶向线粒体和化疗性质。在之前的研究中，我们发现将 Rhodamine 6G 转化为纳米 GUMBOS，即源自一组基于有机盐的均匀材料的纳米材料（GUMBOS），导致癌细胞对化疗的选择性毒性高于正常细胞。在此，我们研究了源自四种不同 Rhodamine 衍生物的 GUMBOS 的化疗活性，其中两种带有酯基，即 Rhodamine 123（R123）和 SNAFR-5，两种带有羧酸基，即 Rhodamine 110（R110）和 Rhodamine B（RB）。在这项研究中，我们评估了（1）通过辛醇-水分配系数评估相对疏水性，（2）细胞毒性和（3）细胞摄取，以评估这些不同化合物之间可能存在的结构-活性关系。有趣的是，我们发现，虽然 R123 和 SNAFR-5 衍生的 GUMBOS 在水性介质中形成纳米 GUMBOS，但 RB 和 R110 GUMBOS 则没有明显的纳米颗粒。进一步的研究表明，R110 和 RB GUMBOS 的相对高水溶性阻碍了纳米颗粒的形成。随后，虽然 R123 和 SNAFR-5 显示出与之前研究的 R6G 纳米 GUMBOS 相似的选择性化疗毒性，但 R110 和 RB GUMBOS 则缺乏这种特性。此外，R123 和 SNAFR-5 纳米 GUMBOS 的化疗毒性也明显大于 R110 和 RB GUMBOS。与 R123 和 SNAFR-5 化合物相比，观察到的细胞摄取减少与 R110 和 RB 的情况一致。此外，这些结果也与之前的观察结果一致，表明纳米颗粒的形成对于观察到的选择性化疗性质以及 Rhodamine 纳米 GUMBOS 的化疗疗效至关重要。
