
Rui Simoes
Rui Simöes, Guest researcher

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