Humans are exposed to flavonoids and isoflavonoids on a daily basis through their diet. Such compounds can be found in fruits, vegetables, herbs, teas, etc. Over the past decade, research into chemical endocrine disruptors has increased. Flavonoids and isoflavonoids also display binding to different receptors throughout human body, which can affect the human endocrine system. With the importance of the glucocorticoid system which controls the metabolism, growth, and stress in mind, the potential binding affinities of selected 40 flavonoids and 35 isoflavonoids to glucocorticoid receptors were researched using in silico methods.
To test for binding affinities, the Virtual ToxLab (VTL) and Endocrine Disruptome (ED) computer programs were used. They are based on anchoring compounds to glucocorticoid receptors. The results were later compared to the data from potential endocrine disruptor databases. Based on the results, flavonoids and isoflavonoids were divided into several groups. The primary research questions were whether the programs predict the binding affinities comparably, and whether the programs adequately predict the binding affinities based on the information obtained from the databases. First, the results were compared with data from databases. The first group included compounds that are found in databases for potential chemical disruptors of the endocrine system and were predicted by both programs to be compounds with high binding affinities. These include the flavonoids baicalein, akacetin, apigenin, luteolin and taxifolin, and the isoflavonoids: coumestrol, glycitein, dalpanin, glabridin and genistein-7-O-β-D glucoside. The second group includes the flavonoids phloretin and hesperetin, both of which belong to the potential chemical disruptors but were not recognized by the programs as compounds with binding affinity to glucocorticoid receptors. The third group includes the compounds that are not present in the databases, but that the programs recognized as compounds with high binding affinity. This group includes flavonoids davidigenin, gossypetin, cianidin, hesperidin and rutin, and the isoflavonoids daidzine, puerarine, glycitin, tectoridine, vestitone, betavulgarine, calycosin, hispaglabridin A. Next, the VTL and ED results were compared. The first group includes only the compound daidzin, which both programs classified as a compound with high binding affinity. The second group includes the flavonoids and isoflavonoids cianidin, hesperidin, neohesperidin, hispaglabridin A, dalpanin, glabridin and genistein-7-O-β-D glucoside, which ED characterized as compounds with middle binding affinity, but VTL characterized as compounds with low binding affinity. The last group is represented by rotenone, which both programs described as a compound with low binding affinity.
In silico methods represent a simple and straightforward way to screen compounds for potential toxicity. However, one must be aware that in silico methods cannot on their own confirm the toxic action of the compound. Based on the results of the programs VTL and ED we suggest further studies for flavonoids and isoflavonoids that demonstrated moderate or high binding affinities: Daidzin, Puerarin, Glycitein, Tectoridin, Cyanidin, Hesperidin, Neohesperidin, Glabridin, Genistein-7-O-β-D-glucoside, Hispaglabridin A and Dalpanin.
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