Synthesis, biological evaluation and molecular docking studies of 2-amino-3,4,5-trimethoxyaroylindole derivatives as novel anticancer agents

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• 作者：Vijay K. Patel ; Harish Rajak ; ^{harishdops@yahoo.co.in" class="auth_mail" title="E-mail the corresponding author}
• 关键词：2-Amino-3 ; 4 ; 5-trimethoxyaroylindole ; Combretastatin A-4 ; Synthesis ; Anticancer
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 May 2016
• 年：2016
• 卷：26
• 期：9
• 页码：2115-2118
• 全文大小：731 K

文摘

A series of novel 2-amino-3,4,5 trimethoxyaroylindole derivatives was synthesized and evaluated against selected human cancer cell lines of breast (MCF-7) and colon (HT-29). Introduction of an amino group at the C-2 position on ring A of 3,4,5-trimethoxyaroylindole derivatives resulted in novel compounds, i.e., 2-amino-3,4,5-trimethoxyaroylindole derivatives exhibiting excellent cytotoxic activity against human cancer cell lines. Substitution with methoxy group at R⁶ in 2-amino-3,4,5-trimethoxyaroylindole 5d exhibited excellent cytotoxic activity against MCF-7 (0.013 μM) and colon HT-29 (0.143 μM) indicating slightly higher potency than Combretastatin A-4. Molecular modeling studies of 2-amino-3,4,5-trimethoxyaroylindole derivatives have similar structural alignment as colchicine in protein (PDB code: 1SA0) and exhibited hydrogen bond interaction between para position of 3,4,5-trimethoxyphenyl ring with CYS 241 and N–H molecule of indole ring with Val 315 of receptor molecule.