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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.)

Design and exploratory data analysis of a second generation of dendrimer prodrugs potentially antichagasic and leishmanicide

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Author(s):
Giarolla, Jeanine [1] ; Mesquita Pasqualoto, Kerly Fernanda [2] ; Ferreira, Elizabeth I. [1]
Total Authors: 3
Affiliation:
[1] Univ Sao Paulo, LAPEN, Dept Pharm, Fac Pharmaceut Sci, BR-05508900 Sao Paulo - Brazil
[2] Butantan Inst, Biochem & Biophys Lab, BR-05503900 Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: MOLECULAR DIVERSITY; v. 17, n. 4, p. 711-720, NOV 2013.
Web of Science Citations: 8
Abstract

Chagas disease and leishmaniasis are neglected tropical diseases, considered as a serious public health. Also, the drugs available for their treatment are toxic and exhibit questionable efficacy. Consequently, the discovery and development of new drug candidates are currently necessary. Dendrimers are highly branched molecules with extremely controlled structure. Those molecular systems display several biological applications (i.e., drug carriers), especially when the focus is prodrug design. Herein, a second generation of dendrimer prodrugs was planned to obtain potentially antichagasic and leishmanicide delivery systems. These dendrimers were composed by myo-inositol (core), l-malic acid (spacer), and three bioactive agents {[}hydroxymethylnitrofurazone (NFOH), quercetin, 3-hydroxyflavone]. The major aim of this study was to investigate the molecular properties (thermodynamics, steric, steric/electronic, electronic, and hydrophobic) to further describe intersamples relationships through either similarity indices or linear combinations of the original variables. Then, an exploratory data analysis, which comprises hierarchical cluster analysis (HCA) and principal components analysis (PCA), was carried out. Complementary findings were observed for PCA and HCA. Steric, intrinsic/steric, steric/electronic, steric/hydrophobic, hydrophobic, and electronic properties influenced the discrimination process. In addition, these molecular properties can also contribute to enzymatic hydrolysis mechanism elucidation, which depends upon the approximation and a subsequent nucleophilic attack to release the drug from the dendrimer prodrugs. (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 type: Scholarships in Brazil - Post-Doctorate