当前位置: X-MOL 学术ChemMedChem › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
In Vivo Anticancer Activity of a Nontoxic Inert Phenolato Titanium Complex: High Efficacy on Solid Tumors Alone and Combined with Platinum Drugs
ChemMedChem ( IF 3.4 ) Pub Date : 2018-10-19 , DOI: 10.1002/cmdc.201800551
Nitzan Ganot 1 , Ori Briaitbard 2 , Asaad Gammal 3 , Joseph Tam 3 , Jacob Hochman 2 , Edit Y. Tshuva 1
Affiliation  

Due to the toxicity of platinum compounds used in the clinic as anticancer chemotherapies, titanium serves as a safe and attractive alternative. Lately, we introduced a new family of Ti complexes based on readily available phenolato ligands, demonstrating incredibly high hydrolytic stability, with the lead compound phenolaTi demonstrating wide cytotoxic activity toward the NCI‐60 panel of human cancer cell lines, with an average GI50 value of 4.7±2 μm. Herein, we evaluated in vivo: a) the safety, and b) the growth inhibitory capacity (efficacy) of this compound. PhenolaTi was found to be effective in vivo against colon (CT‐26) and lung (LLC‐1) murine cell lines in syngeneic hosts and toward a human colon cancer (HT‐29) cell line in immune‐deficient (Nude) mice, with an efficacy similar to that of known chemotherapy. Notably, no clinical signs of toxicity were observed in the treated mice, namely, no effect on body weight, spleen weight or kidney function, unlike the effects observed with the positive control Pt drugs. Studies of combinations of phenolaTi and Pt drugs provided evidence that similar efficacy with decreased toxicity may be achieved, which is highly valuable for medicinal applications.

中文翻译:

无毒惰性苯酚钛复合物的体内抗癌活性:对单独和结合铂类药物的固体肿瘤的高疗效。

由于临床上用作抗癌化学疗法的铂化合物具有毒性,因此钛是安全且有吸引力的替代品。最近,我们引入了一种新的Ti络合物家族,该家族以现成的酚基配体为基础,表现出令人难以置信的高水解稳定性,而铅化合物酚aTi则对人癌细胞系的NCI-60细胞具有广泛的细胞毒活性,平均GI 50值。的4.7±2μ。本文中,我们在体内进行了评估:a)安全性,和b)该化合物的生长抑制能力(功效)。发现PhenolaTi在体内对同系宿主中的结肠(CT-26)和肺(LLC-1)鼠细胞系有效,并在免疫缺陷(Nude)小鼠中对人类结肠癌(HT-29)细胞系有效,具有与已知化学疗法相似的功效。值得注意的是,与阳性对照Pt药物所观察到的效果不同,在所治疗的小鼠中未观察到毒性的临床迹象,即,对体重,脾脏重量或肾脏功能没有影响。酚aTi和Pt药物组合的研究提供了证据,表明可以实现类似的功效,同时降低毒性,这对医学应用具有很高的价值。
更新日期:2018-10-19
down
wechat
bug