In silico study to analyse the disassembly of quercetin-targeted dendrimers potentially leishmanicide

Abstract

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 by myo-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; C₃ in the l-malic acid; and, C₄ nearby the bioactive agent. C₄ seemed to be the most promising carbonyl group to suffer hydrolysis. However, regarding larger molecular systems, such as targeted dendrimers with three branches, C₄ carbonyl group is the most sterically hindered impairing any enzymatic approximation. For this kind of molecular systems, C₁ has presented more spatial accessibility as well as lower electronic density distribution, which are features needed to dendrimer enzymatic disassembly, though.

Keywords::

• molecular modelling
• leishmaniasis
• targeted dendrimer
• dendrimer disassembly

Funding

The authors are grateful to FAPESP (São Paulo Research Foundation) scholarships [07/59416], [10/3651-4], [12/50034-6]; to CNPq (National Council for Scientific and Technological Development); and CAPES (Coordination for Enhancement of Higher Education Personnel) for the financial support; and to the Chem21 Group, Inc., for the MOLSIM 3.2 academic license.

Disclosure statement

No potential conflict of interest was reported by the authors.