Asati Vivek, Mahapatra Debarshi Kar, Bharti Sanjay K
Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur 495009, Chhattisgarh, India.
Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur 495009, Chhattisgarh, India.
Eur J Med Chem. 2014 Nov 24;87:814-33. doi: 10.1016/j.ejmech.2014.10.025. Epub 2014 Oct 12.
A variety of substituents on the thiazolidine-2,4-dione(TZD) nucleus have provided a wide spectrum of biological activities by the using of different mechanism on various target sites. PPARγ ligands have recently been demonstrated to affect cell proliferation, differentiation and apoptosis of different cell types. Currently, some of the TZDs are designed for the treatment of human cancers expressing high levels of PPARγ because it is assumed that activation of PPARγ mediates their anticancer activity. Another site for TZDs is survival signaling pathways under growth factor loops have been implicated in cancer development, progression, and metastasis. The Raf/MEK/ERK, Wnt and PI3K/Akt signalling cascades are the most commonly up-regulated in human cancers. In the present review, various derivatives of thiazolidine-2,4-diones its SAR and different signaling pathways involved to produce anticancer activity been highlighted.
通过作用于不同靶点的不同机制，噻唑烷二酮（TZD）核上的多种取代基展现出了广泛的生物活性。最近有研究表明，PPARγ配体可影响不同细胞类型的细胞增殖、分化和凋亡。目前，一些TZD类药物被设计用于治疗高表达PPARγ的人类癌症，因为人们认为PPARγ的激活介导了它们的抗癌活性。TZD类药物的另一个作用靶点是生长因子环下的生存信号通路，这些通路与癌症的发生、发展和转移有关。Raf/MEK/ERK、Wnt和PI3K/Akt信号级联反应在人类癌症中最常上调。在本综述中，重点介绍了噻唑烷二酮的各种衍生物及其构效关系（SAR），以及产生抗癌活性所涉及的不同信号通路。
