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

Autor(es)

Santos, Soraya da Silva ^[1] ; Giarolla, Jeanine ^[1] ; Pasqualoto, Kerly F. M. ^[2] ; Ferreira, Elizabeth I. ^[1]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR SIMULATION; v. 41, n. 18, p. 1495-1508, DEC 12 2015.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 12/50034-6 - Estudo de liberação de compostos bioativos a partir de pró-fármacos e fármacos dirigidos dendriméricos potencialmente ativos em doenças negligenciadas
• Beneficiário: Jeanine Giarolla Vargas
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado