Groupe SUCRES, UMR 7565, Nancy-Université-CNRS, BP 70239, F-54506 Vandoeuvre-lès-Nancy, France.
Eur J Med Chem. 2012 May;51:206-15. doi: 10.1016/j.ejmech.2012.02.044. Epub 2012 Feb 28.
Breast cancer is the most prevalent cancer in women. The development of resistances to therapeutic agents and the absence of targeted therapy for triple negative breast cancer motivate the search for alternative treatments. With this aim in mind, we synthesised new derivatives of troglitazone, a compound which was formerly used as an anti-diabetic agent and which exhibits anti-proliferative activity on various cancer cell lines. Among the compounds prepared, some displayed micromolar activity against hormone-dependent and hormone-independent breast cancer cells. Furthermore, the influence of the compounds on the viability of primary cultures of human hepatocytes was evaluated. This enabled us to obtain for the first time interesting structure-toxicity relationships in this family of compounds, resulting in 6b and 8b, which show good anti-proliferative activities and poor toxicity towards hepatocytes, compared to troglitazone.
乳腺癌是女性最常见的癌症。治疗药物的耐药性的发展以及三阴性乳腺癌缺乏靶向治疗，这促使人们寻找替代治疗方法。考虑到这一目标，我们合成了曲格列酮的新衍生物，曲格列酮以前曾被用作抗糖尿病药物，并且对各种癌细胞系具有抗增殖活性。在制备的化合物中，一些对激素依赖性和激素非依赖性乳腺癌细胞具有微摩尔活性。此外，还评估了化合物对人原代肝细胞活力的影响。这使我们首次获得了该类化合物的有趣的结构-毒性关系，导致 6b 和 8b 与曲格列酮相比，显示出良好的抗增殖活性和对肝细胞的低毒性。
