LAPEN, Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
J Mol Model. 2012 May;18(5):2257-69. doi: 10.1007/s00894-011-1244-8. Epub 2011 Oct 2.
A molecular modeling study was carried out to investigate the most likely enzymatic disassembly mechanism of dendrimers that were designed as potential antichagasic and antileishmanial prodrugs. The models contained myo-inositol (core), L-malic acid (spacer), and active agents such as 3-hydroxyflavone, quercetin, and hydroxymethylnitrofurazone (NFOH). A theoretical approach that considered one, two, or three branches has already been performed and reported by our research group; the work described herein focused on four (models A and B), five, or six branches, and considered their physicochemical properties, such as spatial hindrance, electrostatic potential mapping, and the lowest unoccupied molecular orbital energy (E(LUMO)). The findings suggest that the carbonyl group next to the myo-inositol is the most promising ester breaking point.
进行了分子建模研究，以调查作为潜在抗恰加斯病和抗利什曼病前药设计的树枝状分子最可能的酶促分解机制。模型包含肌醇（核心）、L-苹果酸（间隔物）和 3-羟基黄酮、槲皮素和羟甲基硝基呋喃酮（NFOH）等活性物质。我们的研究小组已经进行并报告了一种、两种或三种支链的理论方法；本文所述的工作集中在四个（模型 A 和 B）、五个或六个支链，并考虑了它们的物理化学性质，如空间阻碍、静电势映射和最低未占据分子轨道能量 (E(LUMO))。研究结果表明，肌醇旁边的羰基是最有希望的酯断裂点。
