Abstract
The natural product magnolol (1) and a selection of its bioinspired derivatives 2-5, were investigated by Inverse Virtual Screening in order to identify putative biological targets from a panel of 308 proteins involved in cancer processes. By this in silico analysis we selected tankyrase-2 (TNKS2), casein kinase 2 (CK2) and bromodomain 9 (Brd9) as potential targets for experimental evaluations. The Surface Plasmon Resonance assay revealed that 3-5 present a good affinity for tankyrase-2, and, in particular, 3 showed an antiproliferative activity on A549 cells higher than the well-known tankyrase-2 inhibitor XAV939 used as reference compound.
Keywords:
Anti-cancer drugs; Biomimetic compounds; Inverse Virtual Screening; Tankyrase-2; Tankyrase-2 inhibitors.
Copyright © 2018 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Algorithms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Biphenyl Compounds / chemical synthesis
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Biphenyl Compounds / chemistry
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Biphenyl Compounds / pharmacology*
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Cell Proliferation / drug effects
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Dose-Response Relationship, Drug
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Drug Evaluation, Preclinical
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Drug Screening Assays, Antitumor
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Humans
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Lignans / chemical synthesis
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Lignans / chemistry
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Lignans / pharmacology*
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Molecular Structure
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Recombinant Proteins / metabolism
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Structure-Activity Relationship
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Surface Plasmon Resonance
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Tankyrases / antagonists & inhibitors*
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Tankyrases / metabolism
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Thermodynamics
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Tumor Cells, Cultured
Substances
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Antineoplastic Agents
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Biphenyl Compounds
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Lignans
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Recombinant Proteins
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magnolol
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TNKS2 protein, human
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Tankyrases