Manda Bhaskar Reddy, Alla Manjula, Ganji Roopa Jones, Addlagatta Anthony
Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 607, India.
Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 607, India.
Eur J Med Chem. 2014 Oct 30;86:39-47. doi: 10.1016/j.ejmech.2014.08.044. Epub 2014 Aug 13.
A library of structurally diverse Tröger's base analogues has been constructed via unusual amination of methylene bridge employing Vilsmeier-Haack conditions as well as by the incorporation of five and six membered heterocycles on the aromatic core of Tröger's base framework. The constructed structurally diverse frameworks were evaluated for their cytotoxic activities against a panel of three human cancer lines A549 (lung adenocarcinoma), MDAMB-231 (breast) and SK-N-SH (neuroblastoma). From the activity profile obtained, a redesign of Tröger's base analogues led to the construction of more potent molecular entities. The study led to development of a series of compounds with MDAMB-231 cell line specific cytotoxicity. Of the 30 compounds synthesized and evaluated, 7 compounds were found to possess cytotoxicity that is equivalent or better than standard drug doxorubicin against MDAMB-231 cell line while only one compound was found to be active against SK-N-SH cell line.
通过在Vilsmeier-Haack条件下对亚甲基桥进行非同寻常的胺化反应，以及在特罗格碱骨架的芳香核上引入五元及六元杂环，构建了一个结构多样的特罗格碱类似物库。对构建的结构多样的骨架进行了评估，考察它们对三种人类癌细胞系A549（肺腺癌）、MDAMB-231（乳腺癌）和SK-N-SH（神经母细胞瘤）的细胞毒性活性。根据获得的活性概况，对特罗格碱类似物进行重新设计，从而构建出更有效的分子实体。该研究促成了一系列对MDAMB-231细胞系具有特异性细胞毒性的化合物的开发。在合成并评估的30种化合物中，发现有7种化合物对MDAMB-231细胞系具有等同于或优于标准药物阿霉素的细胞毒性，而仅发现一种化合物对SK-N-SH细胞系有活性。
