Investigation of the interactions between flavonoids and human organic anion transporting polypeptide 1B1 using fluorescent substrate and 3D-QSAR analysis was written by Xiang, Yiqun;Liu, Shuai;Yang, Jingjie;Wang, Zhongmin;Zhang, Hongjian;Gui, Chunshan. And the article was included in Biochimica et Biophysica Acta, Biomembranes in 2020.Name: 2′,7′-Dichloro-3′,6′-dihydroxy-3H-spiro[isobenzofuran-1,9′-xanthen]-3-one This article mentions the following:
Organic anion transporting polypeptide 1B1 (OATP1B1) is a key hepatic uptake transporter whose inhibition could lead to adverse drug-drug and drug-food interactions. Flavonoids are widely distributed in food and beverages and thus our bodies are frequently exposed to them. Therefore, investigation of the interactions between OATP1B1 and flavonoids could be of great significance. In the present study, 25 common flavonoids were investigated for their interactions with OATP1B1 using the fluorescent substrate 2′,7′-dichlorofluorescein (DCF) and three-dimensional quant. structure-activity relationship (3D-QSAR) anal. Kinetic study showed that OATP1B1-mediated DCF uptake exhibited a monophasic saturation kinetics with a Km value of 9.7 ± 2.4 μM. Inhibition assay for flavonoids on OATP1B1-mediated DCF uptake was performed and their IC50 values were determined upon which reliable and predictive CoMFA (q2 = 0.604, r2 = 0.841) and CoMSIA (q2 = 0.534, r2 = 0.807) models were developed. Our exptl. and computational results showed that flavonoid aglycons interacted with OATP1B1 much stronger than their glycosides such as 3-O- and 7-O-glycosides as bulky hydrophilic and hydrogen-bond forming substituents at C-3 and C-7 positions on rings A and C were unfavorable for their binding. On the other hand, the presence of hydrogen-bond forming groups on ring B was beneficial as long as the number of hydroxyl groups was not >2. Our results also indicated that flavones usually interacted with OATP1B1 much stronger than their 3-hydroxyflavone counterparts (flavonols). The obtained information and 3D-QSAR models could be useful for elucidating and predicting the interactions between flavonoids and human OATP1B1. In the experiment, the researchers used many compounds, for example, 2′,7′-Dichloro-3′,6′-dihydroxy-3H-spiro[isobenzofuran-1,9′-xanthen]-3-one (cas: 76-54-0Name: 2′,7′-Dichloro-3′,6′-dihydroxy-3H-spiro[isobenzofuran-1,9′-xanthen]-3-one).
2′,7′-Dichloro-3′,6′-dihydroxy-3H-spiro[isobenzofuran-1,9′-xanthen]-3-one (cas: 76-54-0) belongs to benzofurans derivatives. Benzofurans are compounds with a planar structure having 10 pi electrons that include the lone pair on oxygen atom, which makes it more susceptible to electrophilic attack. Substituted benzofurans find applications such as fluorescent sensors, oxidants, in drug discovery, and in another field of chemistry and agriculture.Name: 2′,7′-Dichloro-3′,6′-dihydroxy-3H-spiro[isobenzofuran-1,9′-xanthen]-3-one
Referemce:
Benzofuran – Wikipedia,
Benzofuran | C8H6O – PubChem