Guler Seminay, Kayali Hulya Ayar, Sadan Egemen Orkun, Sen Betul, Subasi Elif
Izmir Biomedicine and Genome Center, Izmir, Turkey.
Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir, Turkey.
Front Pharmacol. 2022 May 10;13:882756. doi: 10.3389/fphar.2022.882756. eCollection 2022.
In this study, we describe the synthesis, characterization and antiproliferative activity of three organo-ruthenium(II) half-sandwich complexes [RuCl(η--cym)(-L)]Cl (I, II, and III). To form these complexes, three thiosemicarbazone ligands (TSCs) were synthesized; L = 5-nitro-2-carboxyaldehyde-thiophen--methyl-thiosemicarbazone, (L1); 2-acetyl-5-bromo-thiophen--methyl-thiosemicarbazone, (L2) and 2-acetyl-5-bromo-thiophen--dimethyl-thiosemicarbazone, (L3). The isolated compounds were analyzed using spectroscopic techniques such as elemental analysis, conductance measurements, FT-IR, H NMR spectroscopy, MALDI-TOF mass spectrometry, and single-crystal XRD. Our results demonstrated that the synthesized thiosemicarbazone ligands (TSCs) are bound to the metal ion as a bidentate ligand that coordinates through the thiocarbonyl sulfur and azomethine nitrogen atoms in all complexes (I, II, and III). The X-ray crystal structures of L1 and L2 revealed that both compounds are crystallized in the triclinic crystal system with space group P-1. The biological potency of newly synthesized TSC ligands (L1, L2, and L3) and their corresponding ruthenium complexes (I, II, and III) were investigated on human primary ovarian (A2780) and human metastatic ovarian (OVCAR-3) cell lines. To get detailed information respecting antitumor properties, cytotoxicity, DNA/BSA binding affinity, cellular uptake, DNA binding competition, and trans-epithelial resistance measurement assays were performed. Our results demonstrate that newly synthesized ruthenium(II) complexes possess potential biological activity. Moreover, we observe that the ruthenium complexes reported here show anticancer activity on primary (A2780) and metastatic (OVCAR-3) ovarian cancer cells.
在本研究中，我们描述了三种有机钌（II）半夹心配合物[RuCl(η⁶-cym)(-L)]Cl（I、II和III）的合成、表征及抗增殖活性。为形成这些配合物，合成了三种硫代氨基脲配体（TSCs）；L = 5-硝基-2-羧基苯甲醛-噻吩-甲基-硫代氨基脲（L1）；2-乙酰基-5-溴-噻吩-甲基-硫代氨基脲（L2）和2-乙酰基-5-溴-噻吩-二甲基-硫代氨基脲（L3）。使用元素分析、电导率测量、傅里叶变换红外光谱（FT-IR）、核磁共振氢谱（¹H NMR）、基质辅助激光解吸电离飞行时间质谱（MALDI-TOF）和单晶X射线衍射（XRD）等光谱技术对分离出的化合物进行了分析。我们的结果表明，合成的硫代氨基脲配体（TSCs）作为双齿配体与金属离子结合，在所有配合物（I、II和III）中通过硫羰基硫和偶氮甲碱氮原子进行配位。L1和L2的X射线晶体结构表明，这两种化合物均以三斜晶系结晶，空间群为P-1。在人原发性卵巢（A2780）和人转移性卵巢（OVCAR-3）细胞系上研究了新合成的TSC配体（L1、L2和L3）及其相应的钌配合物（I、II和III）的生物学活性。为获取有关抗肿瘤特性的详细信息，进行了细胞毒性、DNA/牛血清白蛋白（BSA）结合亲和力、细胞摄取、DNA结合竞争和跨上皮电阻测量试验。我们的结果表明，新合成的钌（II）配合物具有潜在的生物活性。此外，我们观察到此处报道的钌配合物对原发性（A2780）和转移性（OVCAR-3）卵巢癌细胞显示出抗癌活性。
