Esterification of trans-aconitic acid improves its anti-inflammatory activity in LPS-induced acute arthritis
| Autor: | Diego Pinto de Oliveira, José Dias de Souza Filho, Thales do Valle Moreira, Fernão Castro Braga, Nathália Vieira Batista, Flávio A. Amaral, Rodrigo Maia de Pádua, Mauro M. Teixeira |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Male medicine.drug_class Anti-Inflammatory Agents Arthritis Alcohol Pharmacology complex mixtures Anti-inflammatory 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Aconitic acid parasitic diseases medicine Animals Chromatography High Pressure Liquid chemistry.chemical_classification Ethanol Echinodorus grandiflorus biology Esterification Aconitic Acid General Medicine Tricarboxylic acid biology.organism_classification medicine.disease digestive system diseases Kinetics 030104 developmental biology chemistry 030220 oncology & carcinogenesis Lipophilicity Acute Disease |
| Zdroj: | Biomedicinepharmacotherapy = Biomedecinepharmacotherapie. 99 |
| ISSN: | 1950-6007 |
| Popis: | trans-Aconitic acid (TAA) is an abundant constituent in the leaves of Echinodorus grandiflorus, a medicinal plant used to treat rheumatoid arthritis in Brazil. Esterification was explored as a strategy to increase lipophilicity and biopharmaceutical properties of TAA, a highly polar tricarboxylic acid. We herein report the synthesis of TAA esters via Fischer esterification with ethanol, n-butanol and n-octanol. The reaction kinetics was investigated to produce mono-, di- and tri- derivatives. Mono- and diesters of TAA were obtained as a mixture of positional isomers, whereas the triesters were recovered as pure compounds. The obtained esters were screened in a model of acute arthritis induced by the injection of LPS in the knee joint of Swiss mice. The diesters were the most active compounds, regardless of the alcohol employed in the reaction, whereas bioactivity of the derivatives improved by increasing the length of the aliphatic chain of the alcohol employed in esterification. In general, the esters showed higher potency than TAA. When administered orally to mice at doses of 0.017-172.3 μmol/Kg, the diethyl, di-n-butyl and di-n-octyl esters of TAA reduced the cellular infiltration into the knee joint, especially of neutrophils. The study identified diesters of TAA as potential useful derivatives for the management of rheumatoid arthritis and other inflammatory diseases. |
| Databáze: | OpenAIRE |
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