In Silico Evaluation of Ibuprofen and Two Benzoylpropionic Acid Derivatives with Potential Anti-Inflammatory Activity
Metadatos
Mostrar el registro completo del ítemEditorial
MDPI
Materia
Inflammation Molecular docking Molecular dynamics Bioavailability Toxicity
Fecha
2019-04-15Referencia bibliográfica
Bittencourt, J. A., Neto, M. F., Lacerda, P. S., Bittencourt, R. C., Silva, R. C., Lobato, C. C., ... & Borges, R. S. (2019). In Silico Evaluation of Ibuprofen and Two Benzoylpropionic Acid Derivatives with Potential Anti-Inflammatory Activity. Molecules, 24(8), 1476.
Resumen
Inflammation is a complex reaction involving cellular and molecular components and an
unspecific response to a specific aggression. The use of scientific and technological innovations as
a research tool combining multidisciplinary knowledge in informatics, biotechnology, chemistry
and biology are essential for optimizing time and reducing costs in the drug design. Thus, the
integration of these in silico techniques makes it possible to search for new anti-inflammatory
drugs with better pharmacokinetic and toxicological profiles compared to commercially used
drugs. This in silico study evaluated the anti-inflammatory potential of two benzoylpropionic
acid derivatives (MBPA and DHBPA) using molecular docking and their thermodynamic profiles
by molecular dynamics, in addition to predicting oral bioavailability, bioactivity and toxicity.
In accordance to our predictions the derivatives proposed here had the potential capacity for
COX-2 inhibition in the human and mice enzyme, due to containing similar interactions with the
control compound (ibuprofen). Ibuprofen showed toxic predictions of hepatotoxicity (in human,
mouse and rat; toxicophoric group 2-arylacetic or 3-arylpropionic acid) and irritation of the
gastrointestinal tract (in human, mouse and rat; toxicophoric group alpha-substituted propionic
acid or ester) confirming the literature data, as well as the efficiency of the DEREK 10.0.2 program.
Moreover, the proposed compounds are predicted to have a good oral bioavailability profile
and low toxicity (LD50 < 700 mg/kg) and safety when compared to the commercial compound.
Therefore, future studies are necessary to confirm the anti-inflammatory potential of these compounds.