{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:50:11Z","timestamp":1790275811916,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,1,29]],"date-time":"2020-01-29T00:00:00Z","timestamp":1580256000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytochemical Analysis"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Tyrosinase is a multifunctional copper\u2010containing oxidase enzyme that catalyses the first steps in the formation of melanin pigments. Identification of tyrosinase inhibitors is of value for applications in cosmetics, medicine and agriculture.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To develop an analytical method that allows identification of drug\u2010like natural products that can be further developed as tyrosinase inhibitors. Results of\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in silico<\/jats:italic>\n                      studies will be compared in order to gain a deeper insight into the mechanism of action of enzyme inhibition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      Using an\n                      <jats:italic>in vitro<\/jats:italic>\n                      assay we tested tyrosinase inhibitor effects of five structurally related flavones, i.e. luteolin (\n                      <jats:bold>1<\/jats:bold>\n                      ), eupafolin (\n                      <jats:bold>2<\/jats:bold>\n                      ), genkwanin (\n                      <jats:bold>3<\/jats:bold>\n                      ), nobiletin (\n                      <jats:bold>4<\/jats:bold>\n                      ), and chrysosplenetin (\n                      <jats:bold>5<\/jats:bold>\n                      ). The strongest inhibitors were further investigated\n                      <jats:italic>in silico<\/jats:italic>\n                      , using enzyme docking simulations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All compounds tested showed modest tyrosinase inhibitory effect compared to the positive control, kojic acid. The polymethoxy flavones\n                      <jats:bold>4<\/jats:bold>\n                      and\n                      <jats:bold>5<\/jats:bold>\n                      exhibited the strongest tyrosinase inhibitory effect with the half maximal inhibitory concentration (IC\n                      <jats:sub>50<\/jats:sub>\n                      ) values of 131.92 \u00b1 1.75 \u03bcM and 99.87 \u00b1 2.38 \u03bcM respectively. According to kinetic analysis\n                      <jats:bold>2<\/jats:bold>\n                      ,\n                      <jats:bold>4<\/jats:bold>\n                      and\n                      <jats:bold>5<\/jats:bold>\n                      were competitive inhibitors, whereas\n                      <jats:bold>1<\/jats:bold>\n                      and\n                      <jats:bold>3<\/jats:bold>\n                      were non\u2010competitive inhibitors of tyrosinase. Docking studies indicated that methoxy groups on\n                      <jats:bold>4<\/jats:bold>\n                      and\n                      <jats:bold>5<\/jats:bold>\n                      caused steric hindrance which prevented alternative binding modes in the tyrosinase; the methoxy groups on the B\u2010ring of these flavones faced the catalytic site in the enzyme.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The docking simulations nicely complemented the\n                      <jats:italic>in vitro<\/jats:italic>\n                      kinetic studies, opening the way for the development of predictive models for use in drug design.\n                    <\/jats:p>\n                  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