Please use this identifier to cite or link to this item:
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: European Journal of Medicinal Chemistry
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.
Subject: Anti-obesity drugs
Lipid reducing capacity
Small whole-animal model
Zebrafish nile red fluorescence fat metabolism assay
Source: European Journal of Medicinal Chemistry 151 (2018) 272e284
Document Type: Artigo em Revista Científica Internacional
Rights: restrictedAccess
Appears in Collections:CIIMAR - Artigo em Revista Científica Internacional

Files in This Item:
File Description SizeFormat 
  Restricted Access
2.03 MBAdobe PDF    Request a copy

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.