Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 17/A, 43124 Parma, Italy.
Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano, 49, 80131 Napoli, Italy.
Int J Mol Sci. 2024 Oct 9;25(19):10831. doi: 10.3390/ijms251910831.
Research in the field of metallodrugs is continually increasing. However, it is often limited by the poor solubility in water of the metal complexes. To try to overcome this problem, the two new ligands bis-(sodium 3-methoxy-5-sulfonate-salicylaldehyde)thiocarbohydrazone (, NaHL) and bis-(sodium 3-methoxy-5-sulfonate-salicylaldehyde)carbohydrazone (, NaHL) were synthesized and characterized, both achieving high solubility in water. The speciation of the ligands and their coordinating behaviour towards the biologically relevant Cu(II) and Zn(II) ions were studied spectroscopically and potentiometrically, determining the ps of the ligands and the formation constants of the complex species. The monometallic and bimetallic Cu(II) and Zn(II) complexes were isolated, and the single-crystal X-ray structure of [Cu(NaHL)(HO)]3.5HO was discussed. Finally, preliminary studies of the in vitro cytotoxic properties of the new compounds were started on normal (Hs27) and cancer (U937) cell lines. was able to induce a growth inhibition effect between 40% and 45% in both cell lines; did not produce a reduction in cell viability in Hs27 cells but revealed mild antiproliferative activity after 72 h of treatment in U937 cancer cells (GI = 46.5 ± 4.94 μg/mL). Coordination of the Cu(II) ions increased the toxicity of the compounds, while, in contrast, Zn(II) complexes were not cytotoxic.
金属药物领域的研究一直在不断增加。然而，它通常受到金属配合物在水中溶解度差的限制。为了尝试克服这个问题，合成并表征了两种新的配体双-（3-甲氧基-5-磺酸钠水杨醛）硫代缩氨脲（，NaHL）和双-（3-甲氧基-5-磺酸钠水杨醛）缩氨脲（，NaHL），它们都在水中具有高溶解度。配体的形态和它们对生物相关的 Cu(II)和 Zn(II)离子的配位行为通过光谱和电位法进行了研究，确定了配体的 ps 和配合物物种的形成常数。分离出单核和双核 Cu(II)和 Zn(II)配合物，并讨论了[Cu(NaHL)(HO)]3.5HO 的单晶 X 射线结构。最后，开始对正常（Hs27）和癌细胞（U937）系进行新化合物的体外细胞毒性初步研究。能够在两种细胞系中诱导 40%至 45%的生长抑制作用；在 Hs27 细胞中没有降低细胞活力，但在 U937 癌细胞中处理 72 小时后显示出轻度的抗增殖活性（GI = 46.5 ± 4.94 μg/mL）。Cu(II)离子的配位增加了化合物的毒性，而 Zn(II)配合物则没有细胞毒性。
