在静脉注射后对内源性白蛋白结合的醇和氨基结合分子的比较评估
Anja Federa1,2, Hemma Schueffl3, Iris K Minichmayr4
1Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Str. 42, A-1090 Vienna, Austria.
基基硫 (PODS) 提供了一种稳定的替代马莱胺用于结合专蛋白的抗癌药物. 在小鼠中,PODS结合复合体显示出优异的瘤回归和存活率.
科学领域:
- 药用化学 医学化学
- 药物运输 药物运输 药物运输
- 在瘤学瘤学.
背景情况:
- 马利米德是用于将药物与蛋白质结合的常见物质,但患有水解和结合不稳定性.
- 需要更稳定的白蛋白结合单元用于向的癌症药物输送.
- 瘤内源性白蛋白积累是药物输送的关键策略.
研究的目的:
- 为了比较 fenyloxadiazolyl甲基硫 (PODS) 和二甲基硫胺 (DFSA) 衍生物与maleimide作为专结合剂.
- 评估新复合物的水解稳定性和白结合效率.
- 在结肠癌小鼠模型中评估这些复合物的体内疗效.
主要方法:
- 在PODS,DFSA和maleimide的结合中作为氧化-IV) 复合物的配体.
- 评估pH 7.4的水解稳定性和蛋白结合动力学.
- 在CT26结肠癌携带小鼠中进行的药理动力学,生物分布和抗癌疗效研究.
主要成果:
- PODS和DFSA-oxaliplatin复合物表现出比马莱胺类似物更大的水解稳定性.
- PODS和马莱胺显示有效结合白蛋白,而DFSA的结合速度很慢.
- PODS复合物在血清和瘤中达到最高的金水平,导致显著的瘤回归和改善的生存率.
结论:
- PODS是一种有前途的,稳定的替代马莱胺,用于开发结合白蛋白的抗癌药物.
- 与PODS结合的复合体显示出增强的治疗潜力.
- 这项研究验证了PODS作为通过白蛋白结合进行向癌症治疗的优质部分.
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