In silico study to analyse the disassembly of quer... - BV FAPESP
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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Santos, Soraya da Silva [1] ; Giarolla, Jeanine [1] ; Pasqualoto, Kerly F. M. [2] ; Ferreira, Elizabeth I. [1]
Total Authors: 4
Affiliation:
[1] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Pharm, LAPEN, BR-05508 Sao Paulo, SP - Brazil
[2] Butantan Inst, Biochem & Biophys Lab, Sao Paulo, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: MOLECULAR SIMULATION; v. 41, n. 18, p. 1495-1508, DEC 12 2015.
Web of Science Citations: 0
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: C-1, close to the core group; C-2, near the directing group; C-3 in the l-malic acid; and, C-4 nearby the bioactive agent. C-4 seemed to be the most promising carbonyl group to suffer hydrolysis. However, regarding larger molecular systems, such as targeted dendrimers with three branches, C-4 carbonyl group is the most sterically hindered impairing any enzymatic approximation. For this kind of molecular systems, C-1 has presented more spatial accessibility as well as lower electronic density distribution, which are features needed to dendrimer enzymatic disassembly, though. (AU)

FAPESP's process: 12/50034-6 - Bioactive compounds release study from potentially active dendrimer prodrugs and drugs in neglected diseases
Grantee:Jeanine Giarolla Vargas
Support Opportunities: Scholarships in Brazil - Post-Doctoral