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ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

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Research Article

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

Author(s): Muhammed Fatih Karakaya, Faik Gokalp, Erol Sener and Orhan Tansel Korkmaz*

Volume 19, Issue 4, 2023

Published on: 31 March, 2023

Page: [317 - 323] Pages: 7

DOI: 10.2174/1573412919666230313143549

Price: $65

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Abstract

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.

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