0000000000560464
AUTHOR
Francisco Matías Garibotto
3-Chlorotyramine Acting as Ligand of the D2 Dopamine Receptor. Molecular Modeling, Synthesis and D2 Receptor Affinity.
We synthesized and tested 3-chlorotyramine as a ligand of the D2 dopamine receptor. This compound displayed a similar affinity by this receptor to that previously reported for dopamine. In order to understand further the experimental results we performed a molecular modeling study of 3-chlorotyramine and structurally related compounds. By combining molecular dynamics simulations with semiempirical (PM6), ab initio and density functional theory calculations, a simple and generally applicable procedure to evaluate the binding energies of these ligands interacting with the D2 dopamine receptors is reported here. These results provided a clear picture of the binding interactions of these compou…
Polycerasoidol, a Natural Prenylated Benzopyran with a Dual PPARα/PPARγ Agonist Activity and Anti-inflammatory Effect
Dual peroxisome proliferator-activated receptor-α/γ (PPARα/γ) agonists regulate both lipid and glucose homeostasis under different metabolic conditions and can exert anti-inflammatory activity. We investigated the potential dual PPARα/γ agonism of prenylated benzopyrans polycerasoidol (1) and polycerasoidin (2) and their derivatives for novel drug development. Nine semisynthetic derivatives were prepared from the natural polycerasoidol (1) and polycerasoidin (2), which were evaluated for PPARα, -γ, -δ and retinoid X receptor-α activity in transactivation assays. Polycerasoidol (1) exhibited potent dual PPARα/γ agonism and low cytotoxicity. Structure–activity relationship studies revealed th…
Design, synthesis, biological evaluation and molecular modelling of substituted pyrrolo[2,1-a]isoquinolinone derivatives: discovery of potent inhibitors of AChE and BChE
We report here the design, synthesis and biological evaluation of a new series of substituted pyrrolo[2,1-a]isoquinolin-3-one derivatives, some of which have strong inhibitory activity against both AChE and BChE enzymes. The design of these new inhibitors was carried out taking rivastigmine as the starting structure. Thus, on the basis of an exhausting molecular modeling study using combined techniques (docking, dynamic molecular simulations and QTAIM calculations), we obtained new ligands possessing stronger inhibitory effects than rivastigmine, the reference compound. QTAIM analysis gave us detailed information about the molecular interactions stabilizing the different ligand–enzyme compl…