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Rui Simoes. Picture.

Rui Simoes

Rui Simöes, Guest researcher

Rui Simoes. Picture.

Evaluation of biological properties of 3,3',4,4'-benzophenonetetracarboxylic dianhydride derivatives and their ability to inhibit hexokinase activity

Author

  • Krzysztof Kochel
  • Mateusz D Tomczyk
  • Rui F Simões
  • Tomasz Frączek
  • Adrian Soboń
  • Paulo J Oliveira
  • Krzysztof Z Walczak
  • Aneta Koceva-Chyła

Summary, in English

This investigation has explored the properties of 3,3',4,4'-benzophenonetetracarboxylic dianhydride (BDTA) derivatives with regard to their being prospective inhibitors of hexokinase II (HKII). A pluripotent embryonic carcinoma cell line P19 (ECC), was used as the biological target for newly generated potential inhibitors of HKII. The results obtained from Virtual High-Throughput Screening (VHTS), molecular modeling and biological activity studies showed BDTA to be a promising leading structure with a good binding score and simplest functionalization. The inhibitory effect was measured after 72h incubation. Of selected BDTA derivatives, the most active was compound 3b, containing 3-hydroxyphenyl moiety in the para position, being able at 100μM to decrease the mass of differentiated P19dCs cells by 30%, changing both the mitochondrial transmembrane potential and reactive oxygen species level. Under these conditions, only compound 3b had the ability to decrease hexokinase activity in a dose-dependent manner.

Publishing year

2017-02-01

Language

English

Pages

427-431

Publication/Series

Bioorganic & Medicinal Chemistry Letters

Volume

27

Issue

3

Document type

Journal article

Publisher

Elsevier

Topic

  • Medicinal Chemistry
  • Pharmacology and Toxicology

Keywords

  • Animals
  • Apoptosis/drug effects
  • Benzophenones/chemistry
  • Binding Sites
  • Carboxylic Acids/chemical synthesis
  • Cell Line, Tumor
  • Enzyme Inhibitors/chemical synthesis
  • Hexokinase/antagonists & inhibitors
  • Humans
  • Kinetics
  • Membrane Potential, Mitochondrial/drug effects
  • Mice
  • Mitochondria/drug effects
  • Molecular Docking Simulation
  • Protein Structure, Tertiary
  • Reactive Oxygen Species/metabolism

Status

Published

ISBN/ISSN/Other

  • ISSN: 0960-894X