TY - JOUR 
A1 - Bermejo, Almudena
AU - Barrachina, Isabel
AU - El Aouad, Noureddine
AU - Franck, Xavier
AU - Chahboune, Nadia
AU - Andreu, Inmaculada
AU - Figadère, Bruno
AU - Vila, Laura
AU - hennuyer, Nathalie
AU - Staels, Bart
AU - Dacquet, Catherine
AU - Caignard, Daniel H.
AU - Sanz, María-Jesús
AU - Cortés, Diego
AU - Cabedo, Nuria
T1 - Synthesis of benzopyran derivatives as PPARα and/or PPARγ activators
Y1 - 2019
SN - 0968-0896
UR - http://hdl.handle.net/20.500.11939/6461
AB - We describe the synthesis of 26 compounds, small polycerasoidol analogs, that are Lipinski’s rule-of-five compliant. In order to confirm key structural features to activate PPARα and/or PPARγ, we have adopted structural modifications in the following parts: (i) the benzopyran core (hydrophobic nucleus) by benzopyran-4-one, dihydrobenzopyran or benzopyran-4-ol; (ii) the side chain at 2-position by shortening to C3, C4 and C5-carbons versus C-9-carbons of polycerasoidol; (iii) the carboxylic group (polar head) by oxygenated groups (hydroxyl, acetoxy, epoxide, ester, aldehyde) or non-oxygenated motifs (allyl and alkyl). Benzopyran-4-ones 6, 12, 13 and 17 as well as dihydrobenzopyrans 22, 24 and 25 were able to activate hPPARα, whereas benzopyran-4-one (7) with C5-carbons in the side chain exhibited hPPARγ agonism. According to our previous docking studies, SAR confirm that the hydrophobic nucleus (benzopyran-4-one or dihydrobenzopyran) is essential to activate PPARα and/or PPARγ, and the flexible linker (side alkyl chain) should containg at least C5-carbon atoms to activate PPARγ. By contrast, the polar head (“carboxylic group”) tolerated several oxygenated groups but also non-oxygenated motifs. Taking into account these key structural features, small polycerasoidol analogs might provide potential active molecules useful in the treatment of dyslipidemia and/or type 2 diabetes.
KW - Polycerasoidol
KW - PPARα agonism
KW - PPARγ agonism
KW - F60  Plant physiology and biochemistry
KW - Benzopyrene
LA - en
PB - Elsevier
ER -