Sharma Bharvi, Singh Amandeep, Gu Liang, Saha Sourav Taru, Singh-Pillay Ashona, Cele Nosipho, Singh Parvesh, Kaur Mandeep, Kumar Vipan
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
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。
