Screening of Some Plant-Derived Alkaloids and Phenolics for Catechol-OMethyltransferase Inhibition

Abstract

The purpose of this study was to screen natural compounds extracted from plant species (Peganum harmala, Pistacia
terebinthus, Sarcopterium spinosum, Pistacia lentiscus, Hypericum empetrifolium) as medicine alternates in order to
investigate the inhibition characteristics on catechol-O-methyltransferase (COMT) activity. Enzyme activity and inhibition
assays were performed flourometrically where S-adenosylmethionine (SAM) and Aesculetin (ES) were used as methyl
donor and acceptor substrates, respectively. The Km values of SAM and ES were determined as 3.5 ± 0.3 µM and 6.4 ± 0.4
µM in absence of inhibitor, respectively. Inhibition performances of the natural, plant derived polyphenolics and alkaloids
were determined and found that alkaloids extracted from P. harmala seeds showed the strongest inhibition as well as 3,5-
dinitrocatechol (3,5-DNC), positive control. Inhibition mechanism of alkaloids was defined with tight binding
uncompetitive Michaelis-Menten approach like 3,5-DNC. However, the inhibition types of polyphenolic extracts were
found as mixed type inhibitors according to the Michaelis plots their Ki values were determined.