单功能顺式抗癌配合物[Pt(NH3)2(n7 -鸟苷/2′-脱氧鸟苷)X] (X = Cl, Br, I)的合成、结构表征及细胞毒性评价

IF 3.5 3区 化学 Q2 CHEMISTRY, INORGANIC & NUCLEAR
Asjad Ali, Gianluca Rovito, Erika Stefàno, Federica De Castro, Giuseppe Ciccarella, Danilo Migoni, Elisa Panzarini, Antonella Muscella, Santo Marsigliante, Michele Benedetti, Francesco Paolo Fanizzi
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引用次数: 0

摘要

合成了一系列新的单官能团铂(II)配合物顺式-[Pt(NH₃)₂(n7 -鸟苷/2′-脱氧鸟苷)X] (X = Cl, Br, I),并用核磁共振、质谱和icp -原子发射光谱对其进行了表征。这些复合物旨在解决传统双功能铂类药物的局限性,如顺铂,包括细胞毒性和对癌细胞的选择性问题。通过加入鸟苷或2 ' -脱氧鸟苷配体和不同的卤代取代基,研究了结构修饰如何影响不同类似物的选择性和细胞毒性。为了评估新合成的铂衍生物的抗癌潜力,我们对不同的癌细胞系进行了测试,包括肾癌(Caki-1)、宫颈癌(HeLa)、乳腺癌(MCF-7)、淋巴瘤(Raji)和间皮瘤(ZL-34)。此外,通过将其与健康的、永生化的HK-2细胞系(一种来自正常成年男性肾脏的近端小管细胞系)的细胞毒性作用进行比较,评估了对肿瘤细胞的选择性。细胞毒性分析显示,溴代Pt(II)复合物在几种癌细胞系中表现出优越的细胞毒性,特别是在HeLa和Raji细胞中,与氯代和碘取代的复合物相比。碘复合物对MCF-7乳腺癌细胞表现出更高的疗效,表明其具有肿瘤特异性选择性。值得注意的是,与大多数测试的癌细胞系相比,这些复合物在健康细胞中显示出较低的细胞毒性,这反映在相对于顺铂的普遍有利的选择性指数(SI)上。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Synthesis, Structural Characterization, and Cytotoxic Evaluation of Monofunctional cis-[Pt(NH3)2(N7-guanosine/2’-deoxyguanosine)X] (X = Cl, Br, I) Complexes with Anticancer Potential
A series of new monofunctional platinum(II) complexes of the type cis-[Pt(NH₃)₂(N7-guanosine/2’-deoxyguanosine)X] (X = Cl, Br, I) were synthesized and characterized using NMR spectroscopy, mass spectrometry, and ICP-atomic emission spectroscopy. These complexes are designed to address the limitations of conventional bifunctional platinum-based drugs, such as cisplatin, which include issues with cytotoxicity and selectivity towards cancer cells. By incorporating guanosine or 2’-deoxyguanosine ligands and varying halido substituents, the study investigated how structural modifications influence the selectivity and cytotoxicity of the different analogues. To evaluate the anticancer potential of the newly synthesized platinum derivatives, various cancer cell lines were tested, including renal (Caki-1), uterine cervix (HeLa), breast (MCF-7), lymphoma (Raji), and mesothelioma (ZL-34). Additionally, selectivity against tumor cells was assessed by comparing their cytotoxic effects to those in the healthy, immortalized HK-2 cell line, a proximal tubular cell line derived from a normal human adult male kidney. Cytotoxicity analysis revealed that bromido-substituted Pt(II) complexes exhibited superior cytotoxicity across several cancer cell lines, particularly in HeLa and Raji cells, compared to their chlorido- and iodido-substituted counterparts. The iodido complexes exhibited higher efficacy against MCF-7 breast cancer cells, suggesting tumor-specific selectivity. Notably, these complexes demonstrated lower cytotoxicity in healthy cells compared to most of the tested cancer cell lines, as reflected by generally favorable selectivity indices (SI) relative to cisplatin.
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来源期刊
Dalton Transactions
Dalton Transactions 化学-无机化学与核化学
CiteScore
6.60
自引率
7.50%
发文量
1832
审稿时长
1.5 months
期刊介绍: Dalton Transactions is a journal for all areas of inorganic chemistry, which encompasses the organometallic, bioinorganic and materials chemistry of the elements, with applications including synthesis, catalysis, energy conversion/storage, electrical devices and medicine. Dalton Transactions welcomes high-quality, original submissions in all of these areas and more, where the advancement of knowledge in inorganic chemistry is significant.
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