| Abstrakt: |
Molecular modelling methods were previously applied to obtain information regarding the disassembly of the first generation quercetin-targeted dendrimers potentially leishmanicide. Dendrimers containing one to three branches were designed, and their three-dimensional molecular models were built up. They were constituted bymyo-inositol (core and directing group),d-mannose (directing group),l-malic acid (spacer) and quercetin (bioactive agent). Physicochemical properties, such as spatial hindrance, electrostatic potential mapping and the lowest unoccupied molecular orbital energy, were evaluated. Hence, the main purpose of this study was to identify which carbonyl group was the most vulnerable to undergo chemical or enzymatic action. The carbonyl groups were named according to their positions in dendrimer systems as follows: C1, close to the core group; C2, near the directing group; C3in thel-malic acid; and, C4nearby the bioactive agent. C4seemed to be the most promising carbonyl group to suffer hydrolysis. However, regarding larger molecular systems, such as targeted dendrimers with three branches, C4carbonyl group is the most sterically hindered impairing any enzymatic approximation. For this kind of molecular systems, C1has presented more spatial accessibility as well as lower electronic density distribution, which are features needed to dendrimer enzymatic disassembly, though. [ABSTRACT FROM AUTHOR] |
