Flavones as tyrosinase inhibitors: kinetic studies in vitro and in silico.

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dc.cclicenceCC-BY-NCen
dc.contributor.authorSari, Suat
dc.contributor.authorBarut, Burak
dc.contributor.authorArroo, R. R. J.
dc.contributor.authorOzel, Arzu
dc.contributor.authorRuparelia, K. C.
dc.contributor.authorSohretoglu, Didem
dc.date.acceptance2019-10-09
dc.date.accessioned2020-05-05T14:12:30Z
dc.date.available2020-05-05T14:12:30Z
dc.date.issued2020-01-29
dc.descriptionCollaboration between DMU-Leicester School of Pharmacy (UK), Hacettepe University, Faculty of Pharmacy, Ankara (Turkey) and Karadeniz Technical University, Faculty of Pharmacy, Trabzon (Turkey).en
dc.description.abstractIntroduction – Tyrosinase is a multifunctional copper-containing oxidase enzyme that catalyzes the first steps in the formation of melanin pigments. Identification of tyrosinase inhibitors is of value for applications in cosmetics, medicine and agriculture. Objective – To develop an analytical method that allows identification of drug-like natural products that can be further developed as tyrosinase inhibitors. Results of in vitro and in silico studies will be compared in order to gain a deeper insight into the mechanism of action of enzyme inhibition. Method – Using an in vitro assay we tested tyrosinase inhibitor effects of five structurally related flavones, i.e. luteolin (1), eupafolin (2), genkwanin (3), nobiletin (4), and chrysosplenetin (5). The strongest inhibitors were further investigated in silico, using enzyme docking simulations. Results - All compounds tested showed modest tyrosinase inhibitory effect compared to the positive control, kojic acid. The polymethoxy flavones 4 and 5 exhibited the strongest tyrosinase inhibitory effect with IC50 values of 131.92 ± 1.75 μM and 99.87 ± 2.38 μM respectively. According to kinetic analysis 2, 4 and 5 were competitive inhibitors, whereas 1 and 3 were noncompetitive inhibitors of tyrosinase. Docking studies indicated that methoxy groups on 4 and 5 caused steric hindrance which prevented alternative binding modes in the tyrosinase; the methoxy groups on the B-ring of these flavones faced the catalytic site in the enzyme. Conclusions – The docking simulations nicely complemented the in vitro kinetic studies, opening the way for the development of predictive models for use in drug design.en
dc.funderNo external funderen
dc.identifier.citationArroo, R.R.J., Sari, S., Barut, B., Özel, A,, Ruparelia, K.C., Şöhretoğlu, D. (2020) Flavones as tyrosinase inhibitors: kinetic studies in vitro and in silico. Phytochemical Analysis, 31(3), pp. 314-321.en
dc.identifier.doihttps://doi.org/10.1002/pca.2897
dc.identifier.issn0958-0344
dc.identifier.urihttps://dora.dmu.ac.uk/handle/2086/19570
dc.language.isoenen
dc.peerreviewedYesen
dc.publisherWileyen
dc.researchinstituteLeicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)en
dc.subjectFlavonoidsen
dc.subjectTyrosinaseen
dc.subjectEnzyme kineticsen
dc.subjectMolecular dockingen
dc.titleFlavones as tyrosinase inhibitors: kinetic studies in vitro and in silico.en
dc.typeArticleen

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