Molecular modeling study on the disassembly of dendrimers designed as potential antichagasic and antileishmanial prodrugs. 2012

Jeanine Giarolla, and Kerly F M Pasqualoto, and Daniela G Rando, and Márcio H Zaim, and Elizabeth I Ferreira
LAPEN, Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil. jeaninegiarolla@yahoo.com.br

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.

UI MeSH Term Description Entries
D007294 Inositol An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. Myoinositol,Chiro-Inositol,Mesoinositol,Chiro Inositol
D008293 Malates Derivatives of malic acid (the structural formula: (COO-)2CH2CHOH), including its salts and esters.
D009583 Nitrofurazone A topical anti-infective agent effective against gram-negative and gram-positive bacteria. It is used for superficial WOUNDS AND INJURIES and skin infections. Nitrofurazone has also been administered orally in the treatment of TRYPANOSOMIASIS. Nitrofural,Furacilin,Furacillin,Furacin,Nitrofurazone, Calcium (2:1) Salt
D011355 Prodrugs A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug. Drug Precursor,Drug Precursors,Pro-Drug,Prodrug,Pro-Drugs,Precursor, Drug,Precursors, Drug,Pro Drug,Pro Drugs
D011794 Quercetin A flavonol widely distributed in plants. It is an antioxidant, like many other phenolic heterocyclic compounds. Glycosylated forms include RUTIN and quercetrin. 3,3',4',5,7-Pentahydroxyflavone,Dikvertin
D005419 Flavonoids A group of phenyl benzopyrans named for having structures like FLAVONES. 2-Phenyl-Benzopyran,2-Phenyl-Chromene,Bioflavonoid,Bioflavonoids,Flavonoid,2-Phenyl-Benzopyrans,2-Phenyl-Chromenes,2 Phenyl Benzopyran,2 Phenyl Benzopyrans,2 Phenyl Chromene,2 Phenyl Chromenes
D013816 Thermodynamics A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed) Thermodynamic
D014344 Trypanocidal Agents Agents destructive to the protozoal organisms belonging to the suborder TRYPANOSOMATINA. Trypanocidal Drugs,Trypanocides,Trypanosomicidal Agents,Trypanosomicides,Agents, Trypanocidal,Agents, Trypanosomicidal,Drugs, Trypanocidal
D050091 Dendrimers Tree-like, highly branched, polymeric compounds. They grow three-dimensionally by the addition of shells of branched molecules to a central core. The overall globular shape and presence of cavities gives potential as drug carriers and CONTRAST AGENTS. Dendrimer,Dendritic Compounds,Dendritic Polymers,Dendrons,Compound, Dendritic,Dendritic Compound,Dendritic Polymer,Polymer, Dendritic,Polymers, Dendritic
D055672 Static Electricity The accumulation of an electric charge on a object Electrostatic,Electrostatics,Static Charge,Charge, Static,Charges, Static,Electricity, Static,Static Charges

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