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Open AccessArticle

Inhibition of CpLIP2 Lipase Hydrolytic Activity by Four Flavonols (Galangin, Kaempferol, Quercetin, Myricetin) Compared to Orlistat and Their Binding Mechanisms Studied by Quenching of Fluorescence

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UMR 1208 IATE, Université de Montpellier, 34095 Montpellier, France
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UMR 1208 IATE, Montpellier SupAgro, Place Viala, 34060 Montpellier, France
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UMR 1334 AGAP, INRA, Place Viala, 34060 Montpellier, France
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Département Bio-MV, Université de Montpellier, 34095 Montpellier, France
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UMR 7281 BIP, Aix Marseille Université, CNRS, 31 chemin Joseph Aiguier, 13402 Marseille cedex 09, France
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Author to whom correspondence should be addressed.
Academic Editors: Daisuke Miyoshi, Akio Ojida and Kazuhito Tabata
Molecules 2019, 24(16), 2888; https://doi.org/10.3390/molecules24162888
Received: 15 July 2019 / Revised: 2 August 2019 / Accepted: 5 August 2019 / Published: 8 August 2019
The inhibition of recombinant CpLIP2 lipase/acyltransferase from Candida parapsiolosis was considered a key model for novel antifungal drug discovery and a potential therapeutic target for candidiasis. Lipases have identified recently as potent virulence factors in C. parapsilosis and some other yeasts. The inhibition effects of orlistat and four flavonols (galangin, kaempferol, quercetin and myricetin) characterized by an increasing degree of hydroxylation in B-ring, were investigated using ethyl oleate hydrolysis as the model reaction. Orlistat and kaempferol (14 µM) strongly inhibited CpLIP2 catalytic activity within 1 min of pre-incubation, by 90% and 80%, respectively. The relative potency of flavonols as inhibitors was: kaempferol > quercetin > myricetin > galangin. The results suggested that orlistat bound to the catalytic site while kaempferol interacted with W294 on the protein lid. A static mechanism of interactions between flavonols and CpLIP2 lipase was confirmed by fluorescence quenching analyses, indicating that the interactions were mainly driven by hydrophobic bonds and electrostatic forces. From the Lehrer equation, fractions of tryptophan accessibility to the quencher were evaluated, and a relationship with the calculated number of binding sites was suggested. View Full-Text
Keywords: recombinant CpLIP2 lipase; flavonols; orlistat; fluorescence quenching; inhibition; hydroxylation; tryptophan residues; docking recombinant CpLIP2 lipase; flavonols; orlistat; fluorescence quenching; inhibition; hydroxylation; tryptophan residues; docking
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MDPI and ACS Style

Nasri, R.; Bidel, L.P.R.; Rugani, N.; Perrier, V.; Carrière, F.; Dubreucq, E.; Jay-Allemand, C. Inhibition of CpLIP2 Lipase Hydrolytic Activity by Four Flavonols (Galangin, Kaempferol, Quercetin, Myricetin) Compared to Orlistat and Their Binding Mechanisms Studied by Quenching of Fluorescence. Molecules 2019, 24, 2888.

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