Identification of novel indole based heterocycles as selective estrogen receptor modulator
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Date
2018
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Publisher
Academic Press Inc.
Abstract
In the present study, we have designed and synthesized indole derivatives by coalescing the indole nucleus with chromene carbonitrile and dihydropyridine nucleus. Two compounds 5c and 6d were selected from series I and II after sequential combinatorial library generation, docking, absorption, distribution, metabolism and excretion (ADME) filtering, anti-proliferative activity, cytotoxicity, and ER-? competitor assay kit by utilizing estrogen receptor-? (ER-?) dominant T47D BC cells line and PBMCs (Peripheral Blood Mononuclear Cells). Cell imaging experiment suggested that both the compounds successfully cross cellular biomembrane and accumulate in nuclear, cytoplasmic and plasma membrane region. Semiquantitative RT-PCR and Western blotting experiments further supported that both compounds reduced the expression of mRNA and receptor protein of ER-? thereby preventing downstream transactivation and signaling pathway in T47D cells line. Current findings imply that 5c and 6d represent novel ER-? antagonists and may be used in the development of chemotherapy for the management of BC. ? 2018 Elsevier Inc.
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Keywords
2 amino 4 (1 benzyl 1h indol 2 yl) 5 oxo 5,6,7,8 tetrahydro 4h chromene 3 carbonitrile, 2 amino 4 (1 benzyl 1h indol 2 yl) 5 oxo 7 phenyl 5,6,7,8 tetrahydro 4h chromene 3 carbonitrile, 2 amino 4 (1 benzyl 1h indol 2 yl) 7 methyl 5 oxo 5,6,7,8 tetrahydro 4h chromene 3 carbonitrile, 2 amino 4 (1 benzyl 1h indol 2 yl) 7,7 dimethyl 5 oxo 5,6,7,8 tetrahydro 4h chromene 3 carbonitrile, 2 amino 4 (1 benzyl 1h indol 2 yl) 8,8 dimethyl 5 oxo 5,6,7,8 tetrahydro 4h chromene 3 carbonitrile, 2 amino 7 (benzo
Citation
Singla, R., Prakash, K., Bihari Gupta, K., Upadhyay, S., Dhiman, M., & Jaitak, V. (2018). Identification of novel indole based heterocycles as selective estrogen receptor modulator. Bioorganic Chemistry, 79, 72-88. doi: 10.1016/j.bioorg.2018.04.002