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首页> 外文期刊>Dalton transactions: An international journal of inorganic chemistry >Cytotoxic homoleptic Ti(IV) compounds of ONO-type ligands: synthesis, structures and anti-cancer activity
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Cytotoxic homoleptic Ti(IV) compounds of ONO-type ligands: synthesis, structures and anti-cancer activity

机译：细胞毒性分子Ti（IV）Ono型配体的化合物：合成，结构和抗癌活性

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摘要

Eight Ti(IV) compounds 1-8, of the type [Ti(L-n)(2)] where L-n is a variously substituted dianionic tridentate acylhydrazone, were synthesized by reacting the appropriate hydrazide with 2-hydroxybenzaldehyde or 2'-hydroxyacetophenone and titanium(IV) tetra(isopropoxide) in a 2 : 2 : 1 molar ratio. The solid-state structures of 1-6 and 7 center dot CH2Cl2 were deduced from the single crystal X-ray diffraction data, which indicated that each L2- ligand is fully deprotonated and coordinated to the Ti(IV) cation via the enolic oxygen, the imino nitrogen and the phenolic oxygen atoms (ONO donor set) in an enol tautomeric form, the metal assuming the distorted octahedral geometry. The structures of pro-ligands H2L3 and H2L5 are also reported. All complexes displayed high hydrolytic stability. In vitro cytotoxicity assays towards human ovarian A2780 and colon HT-29 cancer cell lines revealed the activity dependence on the acylhydrazone substituents, with electron-donating groups on the phenolato units enhancing the solubility and promoting cytotoxicity. The lead compound 5 of this study presents IC50 values of 2.5 +/- 0.2 and 4.2 +/- 0.6 mu M for ovarian A2780 and colon HT-29 human cancer cells, respectively.
机译：通过使合适的酰肼与2-羟基苯甲醛或2'-羟基乙酮和钛反应，合成[Ti（LN）（2）（2）（2）型]其中LN的八个Ti（IV）化合物1-8，其中LN是各种取代的Dianionic三乙酰腙合成的（iv）Tetra（异丙氧化物）在2：2：1摩尔比中。从单晶X射线衍射数据中推导出1-6和7中心点CH2Cl2的固态结构，表明每个L2-配体通过烯醇氧全完全脱质并与Ti（IV）阳离子配位，亚氨基氮和酚氧原子（ONO供体组）以烯醇互变异构形式，金属假设扭曲的八面体几何形状。还报道了Pro-配体H2L3和H2L5的结构。所有复合物都显示出高水解稳定性。朝向人卵A2780和结肠HT-29癌细胞系的体外细胞毒性测定揭示了酰基腙取代基的活性依赖性，在酚酸盐单位上具有增强溶解度和促进细胞毒性的电子提供基团。本研究的铅化合物5分别显示卵巢A2780和结肠HT-29人癌细胞的IC 50值为2.5 +/- 0.2和4.2 +/-0.6μm。

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