Please use this identifier to cite or link to this item: https://hdl.handle.net/10216/120455
Author(s): Urbatzka R.
Freitas S.
Palmeira A.
Almeida T.
Moreira J.
Azevedo C.
Afonso C.
Correia-da-Silva M.
Sousa E.
Pinto M.
Vasconcelos V.
Title: Lipid reducing activity and toxicity profiles of a library of polyphenol derivatives
Publisher: Elsevier Masson
Issue Date: 2018
Abstract: Obesity is an increasing epidemic worldwide and novel treatments are urgently needed. Polyphenols are natural compounds derived from plants, which are known in particular for their antioxidant properties. However, some polyphenols were described to possess anti-obesity activities in vitro and in vivo. In this study, we aimed to screen a library of 85 polyphenol derivatives for their lipid reducing activity and toxicity. Compounds were analyzed at 5 μM with the zebrafish Nile red fluorescence fat metabolism assay and for general toxicity in vivo. To improve the safety profile, compounds were screened at 50 μM in murine preadipocytes in vitro for cytotoxicity. Obtained activity data were used to create a 2D-QSAR (quantitative structure activity relationship) model. 38 polyphenols showed strong lipid reducing activity. Toxicity analysis revealed that 18 of them did not show any toxicity in vitro or in vivo. QSAR analysis revealed the importance of the number of rings, fractional partial positively charged surface area, relative positive charge, relative number of oxygen atoms, and partial negative surface area for lipid-reducing activity. The five most potent compounds with EC50 values in the nanomolar range for lipid reducing activity and without any toxic effects are strong candidates for future research and development into anti-obesity drugs. Molecular profiling for fasn, sirt1, mtp and ppary revealed one compound that reduced significantly fasn mRNA expression. © 2018 Elsevier Masson
Subject: 1,2 bis[(3 methylbut 2 en 1 yl)oxy] 9h xanthen 9 one
antiobesity agent
dimethyl 2,2' [(9 oxo 9h xanthene 3,6 diyl) bis(oxy)]diacetate
lipid
messenger RNA
polyphenol derivative
resveratrol
unclassified drug
antiobesity agent
antioxidant
polyphenol
animal experiment
Article
carbon nuclear magnetic resonance
controlled study
cytotoxicity
drug screening
EC50
in vitro study
in vivo study
lipid metabolism
nonhuman
proadipocyte
protein expression
quantitative structure activity relation
structure activity relation
surface area
zebra fish
3T3-L1 cell line
adipocyte
animal
chemistry
drug effect
metabolism
mouse
obesity
preclinical study
3T3-L1 Cells
Adipocytes
Animals
Anti-Obesity Agents
Antioxidants
Drug Evaluation, Preclinical
Lipid Metabolism
Mice
Obesity
Polyphenols
Zebrafish
URI: https://hdl.handle.net/10216/120455
Source: European Journal of Medicinal Chemistry, vol. 151, p. 272-284
Document Type: Artigo em Revista Científica Internacional
Rights: restrictedAccess
Appears in Collections:CIIMAR - Artigo em Revista Científica Internacional

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