Investigation of the Pharmacokinetic Properties and Theoretical Chemical Activities of 7,8-Dihydroxyflavone and 4'-Dimethylamino-7,8-Dihydr-oxyflavone

Karakaya M. F., GÖKALP F., ŞENER E., KORKMAZ O. T.

CURRENT PHARMACEUTICAL ANALYSIS, vol.19, no.4, pp.317-323, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 19 Issue: 4
  • Publication Date: 2023
  • Doi Number: 10.2174/1573412919666230313143549
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Biotechnology Research Abstracts, Chemical Abstracts Core, EMBASE
  • Page Numbers: pp.317-323
  • Anadolu University Affiliated: Yes


Aims Flavonoids naturally exist in plants as secondary metabolites. In this study, the aim is to determine and compare the theoretical and in vivo chemical activities of 7,8-dihydroxyflavone (7,8-DHF) and 4'dimethylamino-7,8-dihydroxyflavone (4'-DMA-7,8-DHF), tyrosine receptor kinase B (TrkB) receptor agonist flavonoid molecules with reported potent neuroprotective effects. Methods The density functional theory (DFT) (RB3LYP) method was used for the theoretical chemical analysis. For the in vivo studies, 6-month-old Wistar rats were used in two groups (n=8). 7,8-DHF and 4'-DMA-7,8-DHF (5 mg/kg) were administered intraperitoneally (ip) to each group. Then, plasma samples were collected by carotid catheterization, and brain samples by the microdialysis technique were collected simultaneously for 12 h from awake rats. The level of 7,8-DHF and 4'-DMA-7,8-DHF in blood and brain samples were analyzed and their pharmacokinetics were determined. Results Theoretical calculations show that 7,8-DHF is slightly more stable than 4'-DMA-7,8-DHF. The in vivo pharmacokinetic results show that the maximum concentration of 7,8-DHF was about 48 ng/mL, whereas it was only 8 ng/mL for 4'-DMA-7,8-DHF. Conclusion Our results suggest that the 4'-DMA-7,8-DHF is more unstable and is more prone to binding to TrkB than 7,8-DHF. On the other hand, the in vivo pharmacokinetic results show that 7,8-DHF is more stable than 4'-DMA-7,8-DHF when it is applied systemically at therapeutic concentrations.