Highly cytotoxic, cyclometalated iridium(III)-5-fluoro-8-quinolinol complexes as cancer cell mitochondriotropic agents,New Journal of Chemistry

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Highly cytotoxic, cyclometalated iridium(III)-5-fluoro-8-quinolinol complexes as cancer cell mitochondriotropic agents
New Journal of Chemistry ( IF 2.7 ) Pub Date : 2020-04-15 , DOI: 10.1039/d0nj00465k
Li-Qin Qin _{1,

2,

3,

4,

5} , Bi-Qun Zou _{6,

7,

8,

9,

10} , Qi-Pin Qin _{1,

2,

3,

4,

5} , Zhen-Feng Wang _{1,

2,

3,

4,

5} , Lin Yang _{1,

2,

3,

4,

5} , Ming-Xiong Tan _{1,

2,

3,

4,

5} , Chun-Jie Liang _{1,

2,

3,

4,

5} , Hong Liang _{6,

7,

8,

9,

10}

Affiliation

Four mononuclear cyclometalated iridium(III) complexes, namely, [Ir(FQ)(L1)₂] (Ir-1), [Ir(FQ)(L2)₂] (Ir-2), [Ir(FQ)(L3)₂] (Ir-3) and [Ir(FQ)(L4)₂]·2CH₃OH (Ir-4) using 5-fluoro-8-quinolinol (H-FQ)-based ligands and [(C^N)₂IrCl(μ-Cl)]₂ precursor have been first synthesised. The two most effective complexes (containing 7,8-benzoquinoline (H-L3) and 1-phenylpyrazole (H-L4)), Ir-3 and Ir-4, kill HeLa cells in the nanomole range, with the IC₅₀ values of 0.170 ± 0.05 and 0.035 ± 0.002 μM, respectively, indicating that they could potentially inhibit HeLa tumour populations at a lower concentration. Encouragingly, Ir-3 and Ir-4 induce HeLa apoptosis, as indicated by the clear changes in the apoptosis-associated proteins; both accumulate to a high extent in the mitochondrial fraction; promote mitochondrial membrane (MMP) depolarisation and loss of MMP; and trigger caspase-mediated mitochondrial dysfunction apoptosis pathways. To the best of our knowledge, this study is the first to synthesize cyclometalated iridium(III)-5-fluoro-8-quinolinol complexes that can function as mitochondrion-targeting anticancer drugs.

中文翻译：

具有细胞毒性的环金属化铱（III）-5-氟-8-喹啉醇配合物作为癌细胞的线粒体药物

四种单核环金属化铱（III）配合物，即[Ir（FQ）（L1）₂ ]（Ir-1），[Ir（FQ）（L2）₂ ]（Ir-2），[Ir（FQ）（L3））₂ ]（Ir-3）和[Ir（FQ）（L4）₂ ]·2CH ₃ OH（Ir-4），使用基于5-氟-8-喹啉醇（H-FQ）的配体和[（C ^ N ）₂ IrCl（μ-Cl）] ₂前驱体已被首先合成。两种最有效的络合物（包含7,8-苯并喹啉（H-L3）和1-苯基吡唑（H-L4）），Ir-3和Ir-4，在纳摩尔范围内杀死HeLa细胞，IC ₅₀值分别为0.170±0.05和0.035±0.002μM，这表明它们可能以较低的浓度抑制HeLa肿瘤种群。令人鼓舞的是，Ir-3和Ir-4诱导HeLa细胞凋亡，正如凋亡相关蛋白的明显变化所表明的那样；两者都在线粒体部分大量积累；促进线粒体膜（MMP）去极化和MMP丢失；并触发半胱天冬酶介导的线粒体功能障碍细胞凋亡途径。据我们所知，该研究是第一个合成可用作线粒体靶向抗癌药物的环金属化铱（III）-5-氟-8-喹啉醇复合物。

更新日期：2020-04-15

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