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含 NNS 钳形配体的 Pd(II) 配合物:揭示对乳腺癌和胰腺癌的强大细胞毒性。

Pd(II) complexes bearing NNS pincer ligands: unveiling potent cytotoxicity against breast and pancreatic cancer.

机构信息

Catalysis and Bioinorganic Research Lab, Department of Chemistry, Deshbandhu College, University of Delhi, New Delhi-110019, India.

Department of Chemistry, University of Delhi, New Delhi-110007, India.

出版信息

Dalton Trans. 2024 Jun 10;53(23):9798-9811. doi: 10.1039/d4dt00282b.

Abstract

The continuously increasing rate of breast cancer is one of the major threats to female health worldwide. Recently, palladium complexes have emerged as impressive candidates with effective biocompatibility and anticancer activities. Hence, in the present study, we report a new series of palladium complexes bearing NNS pincer ligands for cytotoxicity studies. The reaction of thiophenol/4-chlorothiophenol/4-methylthiophenol/4-methoxythiophenol with 2-bromo--quinolin-8-yl-acetamide in the presence of sodium hydroxide in ethanol at 80 °C gave [CHN-NH-C(O)-CH-S-Ar] [Ar = CH (L1), CHCl-4 (L2), CHMe-4 (L3), and CH-OMe-4 (L4)]. The corresponding reaction of L1-L4 with NaPdCl in methanol at room temperature for 3 h resulted in complexes [(L1-H)PdCl] (C1), [(L2-H)PdCl] (C2), [(L3-H)PdCl] (C3), and [(L4-H)PdCl] (C4). All new compounds have been characterized by spectroscopic analyses. The structures of complexes C1, C3, and C4 have also been determined from single-crystal X-ray diffraction data. The cytotoxicities of L1-L4 and C1-C4 have been investigated for breast cancer 4T1 and pancreatic cancer MIA-PaCa-2 cells. The IC50 values for complexes C2 and C3 were observed to be comparable to or higher than those of cisplatin. The stressed morphology and cell death of cancerous cells were successfully observed through cellular morphology analysis and the assessment of cytoskeleton damage.

摘要

乳腺癌发病率的持续上升是全球女性健康的主要威胁之一。最近,钯配合物因其具有有效的生物相容性和抗癌活性而成为令人瞩目的候选药物。因此,在本研究中,我们报告了一系列含有 NNS 钳形配体的新型钯配合物,用于进行细胞毒性研究。在乙醇中,将硫酚/4-氯硫酚/4-甲基硫酚/4-甲氧基硫酚与 2-溴-8-喹啉基乙酰胺在氢氧化钠存在下于 80°C 反应,得到 [CHN-NH-C(O)-CH-S-Ar] [Ar = CH (L1)、CHCl-4 (L2)、CHMe-4 (L3) 和 CH-OMe-4 (L4)]。在室温下,将 L1-L4 与 NaPdCl 在甲醇中反应 3 小时,得到配合物 [(L1-H)PdCl] (C1)、[(L2-H)PdCl] (C2)、[(L3-H)PdCl] (C3) 和 [(L4-H)PdCl] (C4)。所有新化合物均通过光谱分析进行了表征。还通过单晶 X 射线衍射数据确定了配合物 C1、C3 和 C4 的结构。研究了 L1-L4 和 C1-C4 对乳腺癌 4T1 和胰腺癌细胞 MIA-PaCa-2 的细胞毒性。发现配合物 C2 和 C3 的 IC50 值与顺铂相当或更高。通过细胞形态分析和细胞骨架损伤评估,成功观察到癌细胞的应激形态和细胞死亡。

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