用于合理设计四氢-β-咔啉-异吲哚酮缀合物作为抗乳腺癌潜在选择性雌激素受体调节剂的非对映选择性方法。
Diastereoselective approach to rationally design tetrahydro-β-carboline-isatin conjugates as potential SERMs against breast cancer.
作者信息
Sharma Bharvi, Singh Amandeep, Gu Liang, Saha Sourav Taru, Singh-Pillay Ashona, Cele Nosipho, Singh Parvesh, Kaur Mandeep, Kumar Vipan
机构信息
Department of Chemistry, Guru Nanak Dev University Amritsar-143005 India
School of Molecular and Cell Biology, University of the Witwatersrand Private Bag 3, Wits-2050 Johannesburg South Africa
出版信息
RSC Adv. 2019 Mar 28;9(17):9809-9819. doi: 10.1039/c9ra00744j. eCollection 2019 Mar 22.
A series of tetrahydro-β-carboline-isatin conjugates, with varying substituents as well as stereochemistry at C-1 and C-5 position of tetrahydro-β-carboline (THβC) and isatin ring, were prepared and assayed for anti-proliferative efficacy on Estrogen Responsive ER(+) (MCF-7) and ER(-ve) MDA-MB-231 cell-lines. The synthesized scaffolds displayed selective anti-proliferative efficacy against MCF-7 cell-line with the most active conjugate 8b exhibiting an IC value of 37.42 μM, comparable to that of peganumine A, a tetrahydro-β-carboline analogue, isolated from . The synthesized compound 8b was also more potent than the standard drug tamoxifen (IC = 50 μM against MCF-7). The observed activities were further corroborated docking studies in ER-α (PDB ID: 3ERT).
制备了一系列四氢-β-咔啉-异吲哚酮缀合物，其在四氢-β-咔啉（THβC）的C-1和C-5位以及异吲哚酮环上具有不同的取代基和立体化学，并检测了它们对雌激素反应性ER(+)（MCF-7）和ER(-ve) MDA-MB-231细胞系的抗增殖功效。合成的支架对MCF-7细胞系显示出选择性抗增殖功效，活性最强的缀合物8b的IC值为37.42 μM，与从……分离出的四氢-β-咔啉类似物骆驼蓬碱A相当。合成的化合物8b也比标准药物他莫昔芬更有效（对MCF-7的IC = 50 μM）。通过在ER-α（PDB ID：3ERT）中的对接研究进一步证实了观察到的活性。
Zotero 插件