作者
B Sathish Kumar, Amit Kumar, Jyotsna Singh, Mohammad Hasanain, Arjun Singh, Kaneez Fatima, Dharmendra K Yadav, Vinay Shukla, Suaib Luqman, Feroz Khan, Debabrata Chanda, Jayanta Sarkar, Rituraj Konwar, Anila Dwivedi, Arvind S Negi
发表日期
2014/10/30
期刊
European Journal of Medicinal Chemistry
卷号
86
页码范围
740-751
出版商
Elsevier Masson
简介
2-Methoxyestradiol (2ME2) is an investigational anticancer drug. In the present study, 2-alkoxyesters/acid and 2-benzyloxy analogues of estradiol have been synthesized as analogues of 2ME2. Three of the derivatives exhibited significant anticancer activity against human breast cancer cell lines. The best analogue of the series i.e. 24 showed stabilization of tubulin polymerisation process. It was substantiated by confocal microscopy and molecular docking studies where 24 occupied ‘paclitaxel binding pocket’ to stabilize the polymerisation process. Compound 24 significantly inhibited MDA-MB-231 cells (IC50: 7 μM) and induced arrest of cell cycle and apoptosis in MDA-MB-231 cells. In acute oral toxicity, 24 was found to be non-toxic and well tolerated in Swiss albino mice up to 1000 mg/kg dose.
学术搜索中的文章
BS Kumar, A Kumar, J Singh, M Hasanain, A Singh… - European Journal of Medicinal Chemistry, 2014