Albumin Conjugates of Thiosemicarbazone and Imidazole-2-thione Prochelators: Iron Coordination and Antiproliferative Activity.
Albumin Conjugates of Thiosemicarbazone and Imidazole-2-thione Prochelators: Iron Coordination and Antiproliferative Activity.
复制标题
DOI：
10.1002/cmdc.202100278
复制
发表时间：
2021-09-16
期刊：
影响因子：
3.4
通讯作者：
Tomat E
中科院分区：
文献类型：
--
作者：
Sung YS;Wu W;Ewbank MA;Utterback RD;Marty MT;Tomat E
铁在肿瘤进展和转移中的中心作用推动了癌症化疗中铁结合方法的发展。基于二硫化物的螯合剂在细胞摄取时被还原激活，以释放负责铁固定的硫醇螯合剂。在此，三甲基缩氨基硫脲部分和咪唑-2-硫酮杂环被结合在该前驱络合剂设计中。相应的三齿络合剂的铁结合导致2：1配体-金属络合物中低自旋铁中心的稳定。天然质谱学实验表明，亲和剂与牛血清白蛋白形成稳定的二硫键偶联物，从而形成新型的生物偶联剂体系。亚微摩尔水平的抗增殖活性在一组乳腺、卵巢和结直肠癌细胞中被记录下来，而在正常的成纤维细胞中活性显著降低。针对癌细胞铁代谢的改变，二硫化物为基础的促络剂在细胞内还原时被激活以进行金属配位。新型取代氨基硫脲和咪唑-2-硫酮体系共价修饰牛血清白蛋白，形成稳定的生物偶联促进剂。在乳腺、卵巢和结肠细胞系中记录了亚微摩尔水平的抗增殖活性。((推特：))@elistopat((Sonderheft Text：))本文属于与欧洲无机化学杂志联合特别收藏《医学中的金属》。((Achtung：VIP))
The central role of iron in tumor progression and metastasis motivates the development of iron-binding approaches in cancer chemotherapy. Disulfide-based prochelators are reductively activated upon cellular uptake to liberate thiol chelators responsible for iron sequestration. Herein, a trimethyl thiosemicarbazone moiety and the imidazole-2-thione heterocycle are incorporated in this prochelator design. Iron binding of the corresponding tridentate chelators leads to the stabilization of a low-spin ferric center in 2:1 ligand-to-metal complexes. Native mass spectrometry experiments show that the prochelators form stable disulfide conjugates with bovine serum albumin, thus affording novel bioconjugate prochelator systems. Antiproliferative activities at submicromolar levels are recorded in a panel of breast, ovarian and colorectal cancer cells, along with significantly lower activity in normal fibroblasts. Targeting the altered iron metabolism of cancer cells, disulfide-based prochelators are activated for metal coordination upon intracellular reduction. Novel substituted thiosemicarbazone and imidazole-2-thione systems covalently modify bovine serum albumin forming stable bioconjugate prochelators. Antiproliferative activities at submicromolar levels are recorded in breast, ovarian, and colon cell lines. ((Twitter:)) @elisatomat ((Sonderheft Text:)) This article belongs to the joint Special Collection with the European Journal of Inorganic Chemistry, “Metals in Medicine”. ((Achtung: VIP))
登录
查看更多内容
影响因子：
7.3
作者：
Bergeron, RJ;Wiegand, J;Brittenham, GM
通讯作者：
Brittenham, GM
影响因子：
5.4
作者：
Bocedi, Alessio;Cattani, Giada;Ricci, Giorgio
通讯作者：
Ricci, Giorgio
影响因子：
4.6
作者：
Daina A;Michielin O;Zoete V
通讯作者：
Zoete V
影响因子：
3.9
作者：
Akam EA;Utterback RD;Marcero JR;Dailey HA;Tomat E
通讯作者：
Tomat E
影响因子：
7.3
作者：
Kratz, F;M端ller-Driver, R;Unger, C
通讯作者：
Unger, C