Novel naphtho[2,3-b]furan-2,4,9(3H)-trione derivatives as potent ERα inhibitors: design, regioselective synthesis, HMBC-NMR characterization, in silico molecular Docking and ADME studies

新型萘并[2,3-b]呋喃-2,4,9(3H)-三酮衍生物作为强效ERα抑制剂:设计、区域选择性合成、HMBC-NMR表征、计算机分子对接和ADME研究

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Abstract

In this study, novel linear 3-(arylamino)naphtho[2,3-b]furan-2,4,9(3H)-trione derivatives has been synthesized via annulation reaction of 2-hydroxy-1,4-naphthoquinone with aromatic amines and glyoxylic acid monohydrate using p-TSOH as catalyst at ambient temperature for the first time. The mechanism proceeds via an initial intermolecular aldol condensation, subsequent Michael addition, and final intramolecular nucleophilic annulation. The linear or angular configurations of the products was confirmed through (1)-(13) C heteronuclear multiple-bond correlation (HMBC) analysis. To evaluate the inhibitory activity of the synthesized compounds, computational methods such as molecular docking and ADME analysis were employed. Compounds 4h and 4i displayed potent activity against tested estrogen receptor alpha (ERα) as compared to Doxorubicin.

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