Flavonoids from Sideritis Species: Human Monoamine Oxidase (hMAO) Inhibitory Activities, Molecular Docking Studies and Crystal Structure of Xanthomicrol.
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.
Department of Pharmaceutical Botany, Faculty of Pharmacy, Hacettepe University, Ankara 06100, Turkey. fpt@hacettepe.edu.tr.
Fatma Pinar
FP
Turkmenoglu
Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Ankara 06100, Turkey. ipekbaysal@hacettepe.edu.tr.
İpek
İ
Baysal
Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Ankara 06100, Turkey. samiye@hacettepe.edu.tr.
Samiye
S
Ciftci-Yabanoglu
Department of Bioinformatics and Genetics, Faculty of Engineering and Natural Sciences, Cibali Campus, Kadir Has University, Fatih, Istanbul 34083, Turkey. yelekci@khas.edu.tr.
Kemal
K
Yelekci
Science and Technology Application and Research Center, Faculty of Pharmacy, Dicle University, Diyarbakir 21280, Turkey. htemel@dicle.edu.tr.|Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Dicle University, Diyarbakir 21280, Turkey. htemel@dicle.edu.tr.
Hamdi
H
Temel
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Dicle University, Diyarbakir 21280, Turkey. spasa@dicle.edu.tr.
Salih
S
Paşa
Department of Pharmaceutical Botany, Faculty of Pharmacy, Hacettepe University, Ankara 06100, Turkey. nezer@hacettepe.edu.tr.
Nurten
N
Ezer
Department of Pharmacognosy, Faculty of Pharmacy, Near East University, Lefkoşa, Mersin-10, Turkey. ihsan.calis@neu.edu.tr.
İhsan
İ
Çalış
Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Ankara 06100, Turkey. gulberk@hacettepe.edu.tr.
Gulberk
G
Ucar
D018360:Crystallography, X-Ray; D047309:Flavones / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D028321:Plant Preparations / Q000737:chemistry* / Q000494:pharmacology; D031365:Sideritis / Q000378:metabolism*; D013329:Structure-Activity Relationship
D047309:Flavones; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D028321:Plant Preparations; C014049:salvigenin; C462036:xanthomicrol; D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human