Consiglio Nazionale delle Ricerche - Istituto di Chimica della Materia Condensata e di Tecnologie per l'Energia (CNR-ICMATE), Corso Stati Uniti 4, 35127 Padua, Italy.
Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Via F. Marzolo 5, 35131 Padua, Italy.
Dalton Trans. 2024 Mar 5;53(10):4526-4543. doi: 10.1039/d3dt03552b.
A library of homoleptic mononuclear Ga(III) complexes of the general formula [Ga(DTC)], where DTC is an alicyclic or a linear dithiocarbamate chelator, is reported. The complexes were prepared in high yields starting from Ga(NO)·6HO and fully characterized by elemental analysis and IR and NMR spectroscopy. Crystals of five of these complexes were obtained. The antitumor activity of the newly synthesized compounds against a panel of human cancer cell lines was evaluated. The chemical nature of the DTC does not have a marked impact on the structural features of the final compound. X-ray crystal structure analyses revealed that all these complexes have a trigonal prismatic geometry with three identical chelating DTCs coordinating the Ga(III) ion. It is noteworthy that in complex 22, [Ga(NHEt)] (NHEt = -ethyldithiocarbamate), the asymmetric unit is formed by two independent and structurally different molecules. Cellular studies showed that all the synthesized Ga-DTC complexes exhibit marked cytotoxic activity, even against human colon cancer cells that are less sensitive to cisplatin. Among the tested compounds, 6 ([Ga(CEPipDTC)], CEPipDTC = (ethoxycarbonyl)-piperidinedithiocarbamate) and 21 ([Ga(Pr-13)], PR13 = 4 and -(2-ethoxy-2-oxoethyl)--methyldithiocarbamate) are very promising derivatives, but they have no selectivity towards cancer cells. Nevertheless, the obtained data provide a foundation for developing gallium-dithiocarbamate complexes as anticancer agents.
报道了一个具有通式[Ga(DTC)]的同核单核 Ga(III) 配合物的库，其中 DTC 是脂环族或直链二硫代氨基甲酸盐螯合剂。这些配合物是从 Ga(NO)·6HO 出发，以高产率制备的，并通过元素分析、IR 和 NMR 光谱法进行了充分的表征。获得了其中五个配合物的晶体。评估了新合成的化合物对一系列人类癌细胞系的抗肿瘤活性。DTC 的化学性质对最终化合物的结构特征没有明显影响。X 射线晶体结构分析表明，所有这些配合物都具有三角棱柱几何形状，三个相同的螯合 DTC 配位 Ga(III) 离子。值得注意的是，在配合物 22 中，[Ga(NHEt)]（NHEt = -乙硫基氨基甲酸盐），不对称单元由两个独立且结构不同的分子组成。细胞研究表明，所有合成的 Ga-DTC 配合物都表现出明显的细胞毒性活性，即使对顺铂敏感性较低的人结肠癌细胞也是如此。在测试的化合物中，6（[Ga(CEPipDTC)]，CEPipDTC = （乙氧羰基）-哌啶二硫代氨基甲酸盐）和 21（[Ga(Pr-13)]，PR13 = 4- 和 -（2-乙氧基-2-氧代乙基）-N-甲基二硫代氨基甲酸盐）是非常有前途的衍生物，但它们对癌细胞没有选择性。尽管如此，所获得的数据为开发作为抗癌剂的镓-二硫代氨基甲酸盐配合物提供了基础。
