Theoretical Study of the Structural and Electronic Properties of Luteolin and Apigenin Dyes

Amat, Anna; Sgamellotti, Antonio; Fantacci, Simona

doi:10.1007/978-3-540-69839-5_87

Cited by 3 publications

(2 citation statements)

References 46 publications

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“…Regarding the binding mode of 1, phenyl ring B was found to fit into subsite + 1 with its 3'-hydroxyl group establishing a hydrogen-bonding interaction with E/ N 328 (Figure 5 C), the same interaction as that found for OH3 from maltoheptaose Glc (+ 1). Given the near planar geometry of luteolin, [27] 1,4-benzopyrone deviated at subsite + 2, compared to the positioning of maltoheptaose, whereas the positioning of the endocylic oxygen atom from ring C of luteolin mimicked that of the interosidic oxygen atom O1 between Glc (+ 1) and Glc (+ 2) of maltoheptaose. The 1,4-benzopyrone was found to stack onto I 228, the mutation of which by an alanine, cysteine, or proline led to significant enhancement of luteolin monoglucosylation (product 1).…”

Section: Compoundmentioning

confidence: 97%

Extending the Structural Diversity of α‐Flavonoid Glycosides with Engineered Glucansucrases

et al. 2014

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Flavonoids constitute an important class of bioactive molecules, the physicochemical properties of which can be modulated by glucosylation. A structurally guided approach has been used to isolate glucansucrases modified in their acceptor‐binding site and specialized for luteolin glucosylation. Of a small‐size library, we isolate mutants showing up to an 8‐fold increase in flavonoid conversion rate over that observed with the parental enzyme. Di‐ and triglucosylated luteolin derivatives never described before have been obtained. They exhibit 282‐ and 17 708‐fold increases in water solubility, respectively, and are protected from oxidation by the glucosylation reaction. Molecular docking enables insight into the product specificity of the best mutants. These results demonstrate that α‐transglucosylase engineering is a powerful means to generate highly specific catalysts for flavonoid glucosylation and deliver new structural scaffolds with increased bioavailability and high relevance for therapeutic applications.

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Section: Compoundmentioning

confidence: 97%

Extending the Structural Diversity of α‐Flavonoid Glycosides with Engineered Glucansucrases

et al. 2014

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“…Los flavonoides pueden tener glicosilaciones (u otras sustituciones como metilaciones) como sustituyentes de los anillos. No obstante, la flexibilidad conformacional del flavonoide depende de la estructura de los anillos B y C (Amat et al, 2008), la estructura plana del anillo C y las sustituciones en los diferentes anillos, son al parecer las principales características señaladas para la interacción con enzimas como las digestivas (Gonzales et al, 2015).…”

Section: Introductionunclassified

Inhibición de lipasa pancreática por flavonoides: importancia del doble enlace C2=C3 y la estructura plana del anillo C//Inhibition of pancreatic lipase by flavonoids: relevance of the C2=C3 double bond and C-ring planarity

et al. 2020

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Lipasa pancreática es una enzima clave en el metabolismo de lípidos. Los flavonoides son compuestos bioactivos de gran relevancia debido a sus interacciones con enzimas digestivas. Se evaluó la actividad de lipasa pancreática en presencia de flavonoides. Mediante espectroscopía UVVisible se determinó que el mejor inhibidor fue quercetina, seguido de rutina > luteolina > catequina > hesperetina, con valores de IC50 de 10.30, 13.50, 14.70, 28.50 y 30.50 μM, respectivamente. Todos los flavonoides mostraron una inhibición mixta, excepto catequina que mostró una inhibición acompetitiva. La capacidad inhibitoria de los flavonoides se relacionó con propiedades estructurales compartidas entre los distintos flavonoides, como la hidroxilación en las posiciones C5, C7 (anillo A), C2’ y C3’ (anillo B), y el doble enlace entre C2 y C3 (anillo C). Los resultados de inhibición coincidieron con el análisis de la fluorescencia extrínseca. Los estudios de docking molecular indicaron que la interacción entre lipasa pancreática y los flavonoides fue principalmente mediante interacciones hidrofóbicas (pi-stacking). Las interacciones de todos los flavonoides, excepto rutina, se dieron en el mismo sitio (subsitio 1) de la enzima. La insaturación entre C2 y C3 fue determinante para el acomodo de los flavonoides con la enzima, principalmente por interacciones de pi-stacking.ABSTRACTPancreatic lipase is a key enzyme in lipid metabolism. Flavonoids are bioactive compounds obtained from vegetables with big relevance, due to their intrinsic interaction with digestive enzymes. Pancreatic lipase activity was evaluated in the presence of flavonoids, through UV-Vis spectroscopy. All tested flavonoids showed a mixed-type inhibition, except catechin, which showed a uncompetitive inhibition. The best inhibitor was quercetin followed by rutin > luteolin > catechin > hesperetin, with IC50 values of 10.30, 13.50, 14.70, 28.50 and 30.50 μM, respectively. The flavonoids inhibitory capacity was related to structural properties shared between the different flavonoids, such as the hydroxylation at C5, C7 (ring A), C2’ and C3’ (ring B), and the double bond between C2 and C3 (ring C). The inhibition results are in agreement with the extrinsic fluorescence analysis. Molecular docking studies indicated that the interaction between pancreatic lipase and flavonoids was mainly through hydrophobic interactions (pi-stacking). The interactions of all flavonoids, except rutin, occurred at the same enzyme site (subsite 1). Instauration between C2 and C3 was decisive for the arrangement of flavonoids with the enzyme, mainly due to pi-stacking interactions.

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Engineering a branching sucrase for flavonoid glucoside diversification

Malbert

Moulis

Brison

et al. 2018

Sci Rep

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Enzymatic glycosylation of flavonoids is an efficient mean to protect aglycons against degradation while enhancing their solubility, life time and, by extension, their bioavailability which is critical for most of their applications in health care. To generate a valuable enzymatic platform for flavonoid glucosylation, an α-1,2 branching sucrase belonging to the family 70 of glycoside-hydrolases was selected as template and subsequently engineered. Two libraries of variants targeting pair-wise mutations inferred by molecular docking simulations were generated and screened for quercetin glucosylation using sucrose as a glucosyl donor. Only a limited number of variants (22) were retained on the basis of quercetin conversion and product profile. Their acceptor promiscuity towards five other flavonoids was subsequently assessed, and the automated screening effort revealed variants showing remarkable ability for luteolin, morin and naringenin glucosylation with conversion ranging from 30% to 90%. Notably, naringenin and morin, a priori considered as recalcitrant compounds to glucosylation using this α-transglucosylases, could also be modified. The approach reveals the potential of small platforms of engineered GH70 α-transglucosylases and opens up the diversity of flavonoid glucosides to molecular structures inaccessible yet.

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Theoretical Study of the Structural and Electronic Properties of Luteolin and Apigenin Dyes

Cited by 3 publications

References 46 publications

Extending the Structural Diversity of α‐Flavonoid Glycosides with Engineered Glucansucrases

Extending the Structural Diversity of α‐Flavonoid Glycosides with Engineered Glucansucrases

Inhibición de lipasa pancreática por flavonoides: importancia del doble enlace C2=C3 y la estructura plana del anillo C//Inhibition of pancreatic lipase by flavonoids: relevance of the C2=C3 double bond and C-ring planarity

Engineering a branching sucrase for flavonoid glucoside diversification

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