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

Kochel, Krzysztof ; Tomczyk, Mateusz D ; Simões, Rui F LU ; Frączek, Tomasz ; Soboń, Adrian ; Oliveira, Paulo J ; Walczak, Krzysztof Z and Koceva-Chyła, Aneta (2017) In Bioorganic & Medicinal Chemistry Letters 27(3). p.427-431
Abstract

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... (More)

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.

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author
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publishing date
type
Contribution to journal
publication status
published
subject
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
in
Bioorganic & Medicinal Chemistry Letters
volume
27
issue
3
pages
427 - 431
publisher
Elsevier
external identifiers
  • pmid:28063798
  • scopus:85008507462
ISSN
0960-894X
DOI
10.1016/j.bmcl.2016.12.055
language
English
LU publication?
no
id
ea764cc2-8c6b-4958-95b3-eff2b43ec320
date added to LUP
2021-09-21 19:25:20
date last changed
2024-06-01 16:52:32
@article{ea764cc2-8c6b-4958-95b3-eff2b43ec320,
  abstract     = {{<p>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.</p>}},
  author       = {{Kochel, Krzysztof and Tomczyk, Mateusz D and Simões, Rui F and Frączek, Tomasz and Soboń, Adrian and Oliveira, Paulo J and Walczak, Krzysztof Z and Koceva-Chyła, Aneta}},
  issn         = {{0960-894X}},
  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}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{3}},
  pages        = {{427--431}},
  publisher    = {{Elsevier}},
  series       = {{Bioorganic & Medicinal Chemistry Letters}},
  title        = {{Evaluation of biological properties of 3,3',4,4'-benzophenonetetracarboxylic dianhydride derivatives and their ability to inhibit hexokinase activity}},
  url          = {{http://dx.doi.org/10.1016/j.bmcl.2016.12.055}},
  doi          = {{10.1016/j.bmcl.2016.12.055}},
  volume       = {{27}},
  year         = {{2017}},
}