INBIOFIV   26685
INSTITUTO DE BIOPROSPECCION Y FISIOLOGIA VEGETAL
Unidad Ejecutora - UE
artículos
Título:
Inhibition of key enzymes in the inflammatory pathway by hybrid molecules of terpenes and synthetic drugs: In vitro and in silico studies
Autor/es:
ALZATE-MORALES, JANS; ALBERTO, MARÍA ROSA; JIMÉNEZ-ASPEE, FELIPE; PERTINO, MARIANO WALTER; THEODULOZ, CRISTINA; ISLA, MARIA INÉS; SCHMEDA-HIRSCHMANN, GUILLERMO
Revista:
CHEMICAL BIOLOGY & DRUG DESIGN
Editorial:
WILEY-BLACKWELL PUBLISHING, INC
Referencias:
Año: 2018 vol. 93 p. 290 - 299
ISSN:
1747-0277
Resumen:
The aim of this work was to compare the anti-inflammatory activity of compounds prepared from terpenes and the synthetic drugs ibuprofen and naproxen. The anti-inflammatory activity of the hybrid compounds was compared with the activity of the parent compounds. This was accomplished using in vitro inhibition of lipoxygenases (LOX) and COX-2, and in silico docking studies in 15-LOX and COX-2. The synthesized hybrids showed an inhibition of COX-2 and LOX between 9.8%?57.4% and 0.0%?97.7%, respectively. None of the hybrids showed an improvement in the inhibitory effect toward these pro-inflammatory enzymes, compared to the parent terpenes and non-steroidal anti-inflammatory drugs. The docking studies allowed us to predict the potential binding modes of hybrids 6?15 within COX-2 and 15-LOX active sites. The relative affinity of the compounds inside the binding sites could be explained by forming non-covalent interactions with most important and known amino acids reported for those enzymes. A good correlation (r 2  = 0.745) between docking energies and inhibition percentages against COX-2 was found. The high inhibition obtained for compound 10 against COX-2 was explained by hydrogen bond interactions at the enzyme binding site. New synthetic possibilities could be obtained from our in silico models, improving the potency of these hybrid compounds.