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利用 Co(III)-环戊二烯基配合物开发抗癌剂。

Exploiting Co(III)-Cyclopentadienyl Complexes To Develop Anticancer Agents.

机构信息

Centro de Química Estrutural, Institute of Molecular Sciences, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal.

Associate Laboratory i4HB - Institute for Health and Bioeconomy, NOVA School of Science and Technology, NOVA University Lisbon, 2819-516 Caparica, Portugal.

出版信息

Inorg Chem. 2024 Apr 1;63(13):5783-5804. doi: 10.1021/acs.inorgchem.3c03696. Epub 2024 Mar 19.

Abstract

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.

摘要

近年来,金属有机配合物作为抗癌治疗药物引起了广泛关注,旨在克服目前市场上铂类药物的局限性。然而,半夹心型金属有机钴配合物的开发仍鲜有探索。本文合成了四个新型含 N,N-杂环双齿配体和膦配体的钴(III)-环戊二烯基配合物,并通过元素分析、光谱技术和 DFT 方法对其进行了全面表征。通过 MTS 法在结直肠(HCT116)、卵巢(A2780)和乳腺(MDA-MB-231 和 MCF-7)人癌细胞系和健康人细胞系(成纤维细胞)中测定了所有配合物的体外细胞毒性。这些配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,这些配合物在鸡胚卵黄囊膜(YSM)试验中的体内试验中显示出非毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7323/10988555/2d91e3db1b7e/ic3c03696_0017.jpg

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