Preprint Article Version 1 This version is not peer-reviewed

Synthesis, Biological Evaluation and Molecular Docking Studies of the 7-Acetamido Substituted 2-Aryl-5-bromo-3-trifluoroacetylindoles as Potential Inhibitors of Tubulin Polymerization

Version 1 : Received: 3 May 2018 / Approved: 4 May 2018 / Online: 4 May 2018 (07:47:06 CEST)

A peer-reviewed article of this Preprint also exists.

Mphahlele, M.J.; Parbhoo, N. Synthesis, Evaluation of Cytotoxicity and Molecular Docking Studies of the 7-Acetamido Substituted 2-Aryl-5-bromo-3-trifluoroacetylindoles as Potential Inhibitors of Tubulin Polymerization. Pharmaceuticals 2018, 11, 59. Mphahlele, M.J.; Parbhoo, N. Synthesis, Evaluation of Cytotoxicity and Molecular Docking Studies of the 7-Acetamido Substituted 2-Aryl-5-bromo-3-trifluoroacetylindoles as Potential Inhibitors of Tubulin Polymerization. Pharmaceuticals 2018, 11, 59.

Journal reference: Pharmaceuticals 2018, 11, 59
DOI: 10.3390/ph11020059

Abstract

Structurally related 7-acetyl-2-aryl-5-bromoindoles 2ad and the 7-acetamido-2-aryl-5-bromoindoles 4ad as well as their corresponding 3-trifluoroacetyl–substituted derivatives 5ad and 5eh were evaluated for potential antigrowth effect in vitro against the human lung cancer (A549) and cervical cancer (HeLa) cells. All of the 3-trifluoroacetyl–substituted 7-acetamido-2-aryl-5-bromoindoles 5eh were found to be more active against both cell lines when compared to the chemotherapeutic drug, Melphalan. The most active compound 5g induced apoptosis in a caspase dependent manner for both cell lines. Compounds 5eh were found to significantly inhibit tubulin polymerization. Molecular docking of 5g into the colchicine-binding site suggests that the compounds bind to tubulin by different type of interactions including pi-alkyl, amide-pi stacked and alkyl interactions as well as hydrogen bonding with the protein residues to elicit anticancer activity.

Subject Areas

7-acetamido-2-aryl-5-bromoindoles; trifluoroacetylation; cytotoxicity; apoptosis; tubulin polymerization; molecular docking

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