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Molecules. 2015 Apr 23;20(5):7454-73. doi: 10.3390/molecules20057454.

Flavonoids from Sideritis Species: Human Monoamine Oxidase (hMAO) Inhibitory Activities, Molecular Docking Studies and Crystal Structure of Xanthomicrol.

Author information

1
Department of Pharmaceutical Botany, Faculty of Pharmacy, Hacettepe University, Ankara 06100, Turkey. fpt@hacettepe.edu.tr.
2
Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Ankara 06100, Turkey. ipekbaysal@hacettepe.edu.tr.
3
Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Ankara 06100, Turkey. samiye@hacettepe.edu.tr.
4
Department of Bioinformatics and Genetics, Faculty of Engineering and Natural Sciences, Cibali Campus, Kadir Has University, Fatih, Istanbul 34083, Turkey. yelekci@khas.edu.tr.
5
Science and Technology Application and Research Center, Faculty of Pharmacy, Dicle University, Diyarbakir 21280, Turkey. htemel@dicle.edu.tr.
6
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Dicle University, Diyarbakir 21280, Turkey. htemel@dicle.edu.tr.
7
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Dicle University, Diyarbakir 21280, Turkey. spasa@dicle.edu.tr.
8
Department of Pharmaceutical Botany, Faculty of Pharmacy, Hacettepe University, Ankara 06100, Turkey. nezer@hacettepe.edu.tr.
9
Department of Pharmacognosy, Faculty of Pharmacy, Near East University, Lefkoşa, Mersin-10, Turkey. ihsan.calis@neu.edu.tr.
10
Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Ankara 06100, Turkey. gulberk@hacettepe.edu.tr.

Abstract

The inhibitory effects of flavonoids on monoamine oxidases (MAOs) have attracted great interest since alterations in monoaminergic transmission are reported to be related to neurodegenerative diseases such as Parkinson's and Alzheimer's diseases and psychiatric disorders such as depression and anxiety, thus MAOs may be considered as targets for the treatment of these multi-factorial diseases. In the present study, four Sideritis flavonoids, xanthomicrol (1), isoscutellarein 7-O-[6'''-O-acetyl-β-D-allopyranosyl-(1→2)]-β-D-glucopyranoside (2), isoscutellarein 7-O-[6'''-O-acetyl-β-D-allopyranosyl-(1→2)]-6''-O-acetyl-β-D-glucopyranoside (3) and salvigenin (4) were docked computationally into the active site of the human monoamine oxidase isoforms (hMAO-A and hMAO-B) and were also investigated for their hMAO inhibitory potencies using recombinant hMAO isoenzymes. The flavonoids inhibited hMAO-A selectively and reversibly in a competitive mode. Salvigenin (4) was found to be the most potent hMAO-A inhibitor, while xanthomicrol (1) appeared as the most selective hMAO-A inhibitor. The computationally obtained results were in good agreement with the corresponding experimental values. In addition, the x-ray structure of xanthomicrol (1) has been shown. The current work warrants further preclinical studies to assess the potential of xanthomicrol (1) and salvigenin (4) as new selective and reversible hMAO-A inhibitors for the treatment of depression and anxiety.

PMID:
25915461
PMCID:
PMC6272178
DOI:
10.3390/molecules20057454
[Indexed for MEDLINE]
Free PMC Article

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