Publication:
In Silico Evaluation of Ibuprofen and Two Benzoylpropionic Acid Derivatives with Potential Anti-Inflammatory Activity.

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Date

2019-04-11

Authors

Bittencourt, Jose A H M
Neto, Moyses F A
Lacerda, Pedro S
Bittencourt, Renata C V S
Silva, Rai C
Lobato, Cleison C
Silva, Luciane B
Leite, Franco H A
Zuliani, Juliana P
Rosa, Joaquín M C

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MDPI AG
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Abstract

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

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MeSH Terms

Animals
Anti-Inflammatory Agents, Non-Steroidal
Benzoates
Computer Simulation
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Humans
Ibuprofen
Mice
Molecular Docking Simulation
Propionates
Rats

DeCS Terms

Antiinflamatorios no Esteroideos
Benzoatos
Ciclooxigenasa 2
Inhibidores de la Ciclooxigenasa 2
Propionatos

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Keywords

bioavailability, inflammation, molecular docking, molecular dynamics, toxicity

Citation

Bittencourt JAHM, Neto MFA, Lacerda PS, Bittencourt RCVS, Silva RC, Lobato CC, et al.. In Silico Evaluation of Ibuprofen and Two Benzoylpropionic Acid Derivatives with Potential Anti-Inflammatory Activity. Molecules. 2019 Apr 15;24(8):1476.