title: Synthesis, biological evaluation and molecular docking studies of 2-amino-3,4,5-trimethoxyaroylindole derivatives as novel anticancer agents.
abstract: 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 R(6) 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.
authors.affiliation: Medicinal Chemistry Research Laboratory, SLT Institute of Pharmaceutical Sciences, Guru Ghasidas University, Bilaspur 495 009, C.G., India.
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Patel
authors.affiliation: Medicinal Chemistry Research Laboratory, SLT Institute of Pharmaceutical Sciences, Guru Ghasidas University, Bilaspur 495 009, C.G., India. Electronic address: harishdops@yahoo.co.in.
authors.forename: Harish
authors.initials: H
authors.lastname: Rajak
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006801:Humans; D006860:Hydrogen Bonding; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry
chemical_list: C000621056:2-amino-3,4,5-trimethoxyaroylindole; D000970:Antineoplastic Agents; D007211:Indoles; D014404:Tubulin
keywords: 2-Amino-3,4,5-trimethoxyaroylindole; Anticancer; Combretastatin A-4; Synthesis