中性 ((I) 三碳酸复合物与硫供体连接物:抗增殖活性和细胞局部化
Aviva Levina1, Kartika Wardhani1, Liam J Stephens2
1School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia. peter.lay@sydney.edu.au.
Dalton transactions (Cambridge, England : 2003)
|April 18, 2024
概括
新的 ((I) 三碳烯复合体与S-捐赠体连接体显示出作为抗癌剂和有机体探针的潜力. 复合体3b在缺乏醇的癌细胞中表现出抗增殖活性,而复合体1a则局部存在溶解体和线粒体中,用于多式成像.
科学领域:
- 协调化学 协调化学
- 药用无机化学 药用无机化学
- 生物有机化学 生物有机化学
背景情况:
- ((I) 三碳化合物复合物已被用于细胞成像和治疗应用.
- 这些复合体中S-捐赠体配体的探索仍然有限,尽管它们具有潜力.
- 之前的研究强调了水合联复合物的活性.
研究的目的:
- 为了合成和表征新型的 (((I) 三碳复合体,其中包括S-捐赠体连接体.
- 评估这些复合物的细胞吸收,抗增殖活性和细胞局部化.
- 探索它们作为抗癌剂和有机细胞探针的潜力.
主要方法:
- 六个fac-[Re(NN)(CO)3(SR) 复合物的合成和表征.
- 在人类乳腺癌细胞系 (MDA-MB-231,MCF-7) 中评估细胞吸收和抗增殖活性.
- 活细胞共聚焦显微镜用于细胞和器官局部化研究 (与Lysotracker和Mitotracker共同局部化).
主要成果:
- 复合物3b (fac-[Re(CO) 3(phen)
2C(O) OMe)) 在缺乏醇的MDA-MB-231细胞中表现出活性 (IC50 ∼10μM),并且在氨酸存在时保持活性. - 复合物1a (fac-[Re(bipy) ((CO) 3(SC(Me) C(O) OMe)) 主要局部在MDA-MB-231细胞的溶解体中,在长时间暴露后部分迁移到线粒体.
- 总体而言,细胞吸收和抗增殖活动通常低于相关水族复合体,但观察到特定的活动.
结论:
- 复合物3b及其类似物显示出作为抗癌药物的前景,特别是在与硫醇减肥剂联合治疗时.
- 综合体1a是开发为多式成像器官探针的合适候选者,因为它的局部化和独特的成像方式.
- 这项研究扩大了(I) 三碳烯复合体与生物医学应用的S-捐赠体连接体的范围.
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