Evaluation of biological properties of 3,3',4,4'-benzophenonetetracarboxylic dianhydride derivatives and their ability to inhibit hexokinase activity
(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
- Kochel, Krzysztof ; Tomczyk, Mateusz D ; Simões, Rui F LU ; Frączek, Tomasz ; Soboń, Adrian ; Oliveira, Paulo J ; Walczak, Krzysztof Z and Koceva-Chyła, Aneta
- publishing date
- 2017-02-01
- 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
-
- scopus:85008507462
- pmid:28063798
- 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
- 2024-08-10 22:19:41
@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}}, }