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Exploiting Co(III)-Cyclopentadienyl Complexes To Develop Anticancer Agents
Inorganic Chemistry ( IF 4.6 ) Pub Date : 2024-03-19 , DOI: 10.1021/acs.inorgchem.3c03696
João Franco Machado 1 , Sandra Cordeiro 2, 3 , Joana N. Duarte 1 , Paulo J. Costa 4 , Paulo J. Mendes 5 , Maria Helena Garcia 1 , Pedro V. Baptista 2, 3 , Alexandra R. Fernandes 2, 3 , Tânia S. Morais 1
Affiliation  

In recent years, organometallic complexes have attracted much attention as anticancer therapeutics aiming at overcoming the limitations of platinum drugs that are currently marketed. Still, the development of half-sandwich organometallic cobalt complexes remains scarcely explored. Four new cobalt(III)-cyclopentadienyl complexes containing N,N-heteroaromatic bidentate, and phosphane ligands were synthesized and fully characterized by elemental analysis, spectroscopic techniques, and DFT methods. The cytotoxicity of all complexes was determined in vitro by the MTS assay in colorectal (HCT116), ovarian (A2780), and breast (MDA-MB-231 and MCF-7) human cancer cell lines and in a healthy human cell line (fibroblasts). The complexes showed high cytotoxicity in cancer cell lines, mostly due to ROS production, apoptosis, autophagy induction, and disruption of the mitochondrial membrane. Also, these complexes were shown to be nontoxic in vivo in an ex ovo chick embryo yolk sac membrane (YSM) assay.

中文翻译:

利用 Co(III)-环戊二烯基配合物开发抗癌药物

近年来,有机金属配合物作为旨在克服目前市售铂类药物局限性的抗癌疗法而备受关注。尽管如此,半夹心有机金属钴配合物的开发仍然很少被探索。合成了四种含有 N,N-杂芳族二齿和磷烷配体的新型钴(III)-环戊二烯基配合物,并通过元素分析、光谱技术和 DFT 方法对其进行了充分表征。所有复合物的细胞毒性均通过结直肠 (HCT116)、卵巢 (A2780) 和乳腺癌 (MDA-MB-231 和 MCF-7) 人类癌细胞系以及健康人类细胞系(成纤维细胞)中的 MTS 测定进行体外测定。 )。这些复合物在癌细胞系中表现出高细胞毒性,主要是由于 ROS 产生、细胞凋亡、自噬诱导和线粒体膜破坏。此外,在离卵鸡胚卵黄囊膜(YSM)测定中,这些复合物在体内被证明是无毒的。
更新日期:2024-03-19
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