The Synthesis, Metal Exchange, and Hyaluronate Functionalization of a Cationic Gallium-Based Thiosemicarbazone Anticancer Drug

一种阳离子镓基硫代氨基脲抗癌药物的合成、金属交换和透明质酸功能化

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Abstract

We herein demonstrate that the thiosemicarbazone (TSC) ligand N'-(di(pyridin-2-yl)methylene)-4-(thiazol-2-yl)piperazine-1-carbothiohydrazide (HL) can coordinate with Ga(3+) to give cationic complex [Ga(L)(2)]NO(3) featuring an octahedral Ga(III) center. [Ga(L)(2)]NO(3) undergoes metathesis with both Fe(2+) and Fe(3+), resulting in the formation of respective Fe(2+)- and Fe(3+) complexes. [Ga(L)(2)]NO(3) is also susceptible to anion exchange with sodium hyaluronate (NaA) to produce the nanoformulation [Ga(L)(2)]A with boosted aqueous solubility and cell targeting. [Ga(L)(2)]A demonstrated remarkable in vitro cytotoxicity against NCI-H82 and A549 (lung cancer), as well as KYSE-510 and Te-1 (esophageal cancer) cell lines, featuring half maximal inhibitory concentration (IC(50)) values in the range 0.102-2.616 μmol L(-1). This work highlights the potential of using non-toxic and biocompatible Ga(3+) as the central ion to prepare TSC-based nanomedicines for combating cancer.

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